supplementary materials for...mkl-1 rl pant1 uiso rl pant1 survivin α!tubulin figure s1. mcv small...

www.sciencetranslationalmedicine.org/cgi/content/full/4/133/133ra56/DC1

Supplementary Materials for

Survivin Is a Therapeutic Target in Merkel Cell Carcinoma

Reety Arora, Masahiro Shuda, Anna Guastafierro, Huichen Feng, Tuna Toptan, Yanis Tolstov, Daniel Normolle, Laura L. Vollmer, Andreas Vogt, Alexander Dömling, Jeffrey

L. Brodsky, Yuan Chang,* Patrick S. Moore*

*To whom correspondence should be addressed. E-mail: [email protected] (P.S.M.); [email protected] (Y.C.)

Published 9 May 2012, Sci. Transl. Med. 4, 133ra56 (2012) DOI: 10.1126/scitranslmed.3003713

The PDF file includes:

Fig. S1. MCV small T antigen knockdown does not affect survivin expression. Fig. S2. T antigen knockdown does not affect caspase and PARP cleavage. Fig. S3. MCV small T antigen isoform does not induce survivin expression in BJ cells. Fig. S4. MCV large T antigen does not affect survivin oncoprotein expression in U2OS cells. Fig. S5. Bortezomib induces apoptotic cell death in MCC tumor cells. Fig. S6. Dose-response curves for drug screen candidates. Fig. S7. Survivin mRNA in xenograft mice. Table S1. Transcripts in MCC libraries. Table S2. Compound library screen results (data set). Appendix S1. Bayesian hierarchical changepoint analysis of the effect of YM155 and bortezomib on tumor xenograft volume.

MKL-1

sT1

panT

1

shC

ntrl

UISO

sT1

panT

1

shC

ntrl

Survivin

α-‐Tubulin

Figure S1. MCV small T antigen knockdown does not affect survivin expression. UISO and MKL-1 cells infected with sT1, which knockdown sT alone (Shuda et al. JCI, 2011) as well as panT1 shRNA lentiviruses were tested for immunoblotting for survivin and α-tubulin. Lanes were run on the same gel, but were not contiguous.

shC

ntrl

panT

1

MKL-1

α-Tubulin

cCasp9

cPARP

cCasp3

UISO

shC

ntrl

panT

1

Figure S2. T antigen knockdown does not affect caspase and PARP cleavage. UISO and MKL-1 cells with panT1 knockdown were tested for immunoblotting for cleaved caspase 3 and 9, cleaved PARP and α- tubulin. Also see main Figure 1B.

Em

pty

LT.3

39

sT

Survivin

α-‐Tubulin

BJ cells

Figure S3. MCV small T antigen isoform does not induce survivin expression in BJ cells. BJ cells were transduced with either empty vector, tumor derived LT cDNA (LT.339) or small T antigen cDNA and immunoblotted for (A ) survivin and α- tubulin ( B) CM8E6 (MCV T antigen exon 1). Lanes were run on the same gel, but were not contiguous. Also see Main Figure 2.

Em

pty

sT

CM8E6

BJ cells

A B

U2OS

Figure S4. MCV large T antigen does not affect survivin oncoprotein expression in U2OS cells. U2OS cells were transduced and stably selected with empty vector, tumor derived LT cDNA (LT.339) or an LT cDNA with an inactive RB binding domain (LT.339.LFCDK) and immunoblotted for (A) survivin and α- tubulin (LICOR) (B) MCV Large T antigen (using CM2B4 antibody). Lanes were run on the same gel, but were not contiguous.

LT.3

39

Em

pty

LT.3

39.L

FCD

K

α-Tubulin

Survivin MCV LT (CM2B4)

U2OS

LT.3

39

Em

pty

LT.3

39.L

FCD

K

A B

10,000 1000 100 10 1 0

Bortezomib (nM)

8 12 24 48 72 2 0 (hr)

cPARP

α-Tubulin

cCasp3

A B

cPARP

α-Tubulin

cCasp3

MKL-1 MKL-2 MS-1 WaGa UISO

MCV +ve cell lines

Bortezomib 100nM + - + - + - + - + -

cPARP

cCasp3

α -Tubulin

C

Figure S5. Bortezomib induces apoptotic cell death in MCC tum cells. (A) MKL-1 cells were treated with Bortezomib (1, 10, 100, 1000 and 10,000 nM) for 48 h or (B) MKL-1 cells treated with 100 nM bortezomib for different time points, or (C) other MCC cell lines (MKL-1, MKL-2, MS-1, WaGa and UISO) treated with 100 nM bortezomib for 48 h were tested for immunoblotting for cleaved caspase 3, cleaved PARP apoptotic markers and α- tubulin. 0.01% DMSO was used for mock-treatment control.

Bortezomib (100nM)

or

Ellipticine

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

Teniposide

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

Mitoxantrone

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

Doxorubicin

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

Amsacrine hydrochloride

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

Valrubicin

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

Daunorubicin

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

Topotecan

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

Topoisomerase InhibitorsA

Iodoacetamide

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

NSC 95397

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

Calmidazolium chloride

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

Bay 11-7085

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

Sanguinarine chloride

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

Chelerythrine chloride

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

Tetraethylthiuram disulfide

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

Quinacrine dihydrochloride

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120MKL-1

MKL-2

MS-1

WaGa

UISO

Concentration (M)

% S

urv

iva

l

Other DrugsB

C

D E

Bortezomib

10-11 10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120 MKL-1

MKL-2

MS-1

WaGa

UISO

MCC13

MCC26

BJ

BJhTERT

Concentration (M)

% S

urv

iva

l

Oth

er

MC

V -

ve

MC

CM

CV

+ve

MC

C

Bortezomib

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120

293U2OS

NCI-H69

Concentration(M)

% S

urv

iva

l

YM155

10-10 10-9 10-8 10-7 10-6 10-5 10-4 10-30

20

40

60

80

100

120

293U2OS

NCI-H69

Concentration (M)

% S

urv

iva

l

Figure S6. Dose response curves for drug screen candidates. MCC cell lines and other human cancer cell lines were treated with compounds identified from the screen at increasing doses. Cell viability was normalized to no drug conditions (%survival=100). Shown is the average and standard deviation for 2 independent experiments tested in triplicate. (A) Topoisomerase inhibitors (B) other drugs (C) Bortezomib (D) Bortezomib and (E) YM155 tested on NCI-H69, 293 and U2OS cells.

-

Figure S7.Survivin mRNA in xenograft mice. qRT-PCR for survivin from saline and YM155 (2 mg/kg) treated tumor tissues. Column represents mean and error bars represent standard deviation. Experiment was done in triplicate (mean+SEM)

Table S1. Transcripts in MCC libraries

Gene symbol Gene name NCBI Accession

MCC347 Library

MCC337.343.346 Library

Normalized ratio Log2 value #

(MCV +ve)* (MCV -‐ve)* (MCV +ve / MCV -‐ve)

Apotosis-‐associated genesBIRC5 Baculoviral IAP repeat containing 5 NM_001012271 17 2 6.79 2.76DFFB DNA fragmentation factor, 40kDa, beta polypeptide (caspase-‐activated DNase) NM_004402 7 1 5.59 2.48CHUK Conserved helix-‐loop-‐helix ubiquitous kinase NM_001278 7 1 5.59 2.48ENDOG Endonuclease G NM_004435 6 1 4.79 2.26AIFM1 Apoptosis-‐inducing factor, mitochondrion-‐associated, 1 NM_145813 9 2 3.59 1.85PPP3CA Protein phosphatase 3, catalytic subunit, alpha isozyme NM_000944 36 8 3.59 1.85BIRC2 Baculoviral IAP repeat containing 2 NM_001166 8 2 3.19 1.68CASP10 Caspase 10, apoptosis-‐related cysteine peptidase NM_032977 8 2 3.19 1.68ATM Ataxia telangiectasia mutated NM_138292 37 10 2.96 1.56TNFRSF1A Tumor necrosis factor receptor superfamily, member 1A NM_001065 19 6 2.53 1.34IRAK2 Interleukin-‐1 receptor-‐associated kinase 2 NM_001570 3 1 2.40 1.26MYD88 Myeloid differentiation primary response gene (88) NM_002468 6 2 2.40 1.26PRKAR2B Protein kinase, cAMP-‐dependent, regulatory, type II, beta NM_002736 3 1 2.40 1.26PIK3R3 Phosphoinositide-‐3-‐kinase, regulatory subunit 3 (gamma) NM_003629 15 6 2.00 1.00CHP Calcium binding protein P22 NM_007236 12 5 1.92 0.94BCL2 B-‐cell CLL/lymphoma 2 NM_000657 2 1 1.60 0.68CASP3 Caspase 3, apoptosis-‐related cysteine peptidase NM_032991 4 2 1.60 0.68TRADD TNFRSF1A-‐associated via death domain NM_003789 2 1 1.60 0.68ENDOD1 Endonuclease domain containing 1 NM_015036 11 6 1.46 0.55MAP3K14 Mitogen-‐activated protein kinase kinase kinase 14 NM_003954 8 5 1.28 0.35PRKAR1A Protein kinase, cAMP-‐dependent, regulatory, type I, alpha NM_212472 48 30 1.28 0.35PRKX Protein kinase, X-‐linked NM_005044 8 5 1.28 0.35CAPN1 Calpain 1, (mu/I) large subunit NM_005186 18 12 1.20 0.26PIK3R2 Phosphoinositide-‐3-‐kinase, regulatory subunit 2 (beta) NM_005027 61 43 1.13 0.18CYCS Cytochrome c, somatic NM_018947 51 40 1.02 0.03DFFA DNA fragmentation factor, 45kDa, alpha polypeptide NM_213566 23 18 1.02 0.03RIPK1 Receptor (TNFRSF)-‐interacting serine-‐threonine kinase 1 NM_003804 12 10 0.96 -‐0.06AKT2 v-‐akt murine thymoma viral oncogene homolog 2 NM_001626 23 20 0.92 -‐0.12APAF1 Apoptotic peptidase activating factor 1 NM_013229 8 7 0.91 -‐0.13PRKY Protein kinase, Y-‐linked, pseudogene NM_002760 9 8 0.90 -‐0.15AKT1 v-‐akt murine thymoma viral oncogene homolog 1 NM_001014432 36 34 0.85 -‐0.24CASP7 Caspase 7, apoptosis-‐related cysteine peptidase NM_033338 2 2 0.80 -‐0.32EXOG Endo/exonuclease (5'-‐3'), endonuclease G-‐like NM_005107 1 1 0.80 -‐0.32IRAK4 Interleukin-‐1 receptor-‐associated kinase 4 NM_016123 5 5 0.80 -‐0.32NTRK1 Neurotrophic tyrosine kinase, receptor, type 1 NM_001012331 1 1 0.80 -‐0.32PIK3CB Phosphoinositide-‐3-‐kinase, catalytic, beta polypeptide NM_006219 4 4 0.80 -‐0.32PPP3CB Protein phosphatase 3, catalytic subunit, beta isozyme NM_021132 15 15 0.80 -‐0.32TNFRSF10B Tumor necrosis factor receptor superfamily, member 10b NM_147187 2 2 0.80 -‐0.32cIAP2 Cellular inhibitor of apoptosis 2 NM_001165 1 1 0.80 -‐0.32IKBKG Inhibitor of kappa light polypeptide gene enhancer in B-‐cells, kinase gamma NM_001099857 8 9 0.71 -‐0.49BCL2L1 BCL2-‐like 1 NM_138578 24 28 0.68 -‐0.55PRKACB Protein kinase, cAMP-‐dependent, catalytic, beta NM_002731 11 13 0.68 -‐0.57PRKACA Protein kinase, cAMP-‐dependent, catalytic, alpha NM_207518 25 31 0.64 -‐0.63CFLAR CASP8 and FADD-‐like apoptosis regulator NM_003879 5 8 0.50 -‐1.00PIK3CA Phosphoinositide-‐3-‐kinase, catalytic, alpha polypeptide NM_006218 3 4 0.60 -‐0.74PPP3R1 Protein phosphatase 3, regulatory subunit B, alpha NM_000945 6 8 0.60 -‐0.74TP53 Tumor protein p53 NM_000546 15 21 0.57 -‐0.81BAX BCL2-‐associated X protein NM_138761 2 3 0.53 -‐0.91PIK3CD Phosphoinositide-‐3-‐kinase, catalytic, delta polypeptide NM_005026 2 3 0.53 -‐0.91PRKAR1B Protein kinase, cAMP-‐dependent, regulatory, type I, beta NM_002735 3 5 0.48 -‐1.06XIAP X-‐linked inhibitor of apoptosis protein NM_001167 10 18 0.44 -‐1.17CASP9 Caspase 9, apoptosis-‐related cysteine peptidase NM_032996 1 2 0.40 -‐1.32BID BH3 interacting domain death agonist NM_197967 1 2 0.40 -‐1.32CHP2 Calcineurin B homologous protein 2 NM_022097 1 2 0.40 -‐1.32NFKBIA Nuclear factor of kappa light polypeptide gene enhancer in B-‐cells inhibitor, alpha NM_020529 10 22 0.36 -‐1.46IL1R1 Interleukin 1 receptor, type I NM_000877 3 7 0.34 -‐1.55IKBKB Inhibitor of kappa light polypeptide gene enhancer in B-‐cells, kinase beta NM_001556 5 12 0.33 -‐1.59AKT3 v-‐akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) NM_005465 2 5 0.32 -‐1.65CASP6 Caspase 6, apoptosis-‐related cysteine peptidase NM_001226 2 5 0.32 -‐1.65BAD BCL2-‐associated agonist of cell death NM_032989 5 13 0.31 -‐1.70IRAK1 Interleukin-‐1 receptor-‐associated kinase 1 NM_001025243 9 24 0.30 -‐1.74NFKB1 Nuclear factor of kappa light polypeptide gene enhancer in B-‐cells 1 NM_003998 1 3 0.27 -‐1.91PIK3R1 Phosphoinositide-‐3-‐kinase, regulatory subunit 1 (alpha) NM_181504 3 9 0.27 -‐1.91PPP3CC Protein phosphatase 3, catalytic subunit, gamma isozyme NM_005605 2 9 0.18 -‐2.49CAPN2 Calpain 2, (m/II) large subunit NM_001748 3 21 0.11 -‐3.13TRAF2 TNF receptor-‐associated factor 2 NM_021138 1 11 0.07 -‐3.78Control genesACTB Actin, beta NM_001101 544 668 0.65 -‐0.62B2M Beta-‐2-‐microglobulin NM_004048 94 60 1.25 0.32CK20 Keratin 20 NM_019010 15 13 0.92 -‐0.12GAPDH Glyceraldehyde-‐3-‐phosphate dehydrogenase NM_002046 438 228 1.53 0.62HPRT1 Hypoxanthine phosphoribosyltransferase 1 NM_000194 7 9 0.62 -‐0.69PPIA Peptidylprolyl isomerase A (cyclophilin A) NM_021130 143 75 1.52 0.61* "MCV +ve" stands for MCV positive in the MCC347 library with 143,373 gene reads; "MCV -‐ve" stands for MCV negative in the MCC337.343.346 library with 114,514 gene reads# "+" stands for gene upregulation in the "MCV +ve" library compared with the "MCV -‐ve" one; "-‐" stands for gene downregulation ratios. (Feng et al. Science 319:1096-‐100, 2008).

Correspondence should be addressed P.S.M ([email protected]) or Y.C. ([email protected])

Sigma Catalog # Name Description / Mechanism of Action Class % Survival

Index

C 59827-Chloro-4-hydroxy-2-phenyl-1,8-naphthyridine

A1 adenosine receptor antagonist Adenosine 64.1

I 5879 3-Isobutyl-1-methylxanthine

Potent phosphodiesterase inhibitor; more active than theophylline at adenosine receptors Adenosine 70.9

C-197 8-(3-Chlorostyryl)caffeine Selective A2A adenosine receptor antagonist Adenosine 81.3

A-0138-(p-Sulfophenyl)theophylline

Adenosine receptor antagonist with selectivity for A1 over A2 Adenosine 84.1

C 5134 2-Chloroadenosine Adenosine receptor agonist with selectivity for A1 over A2 Adenosine 84.3

P 2278 1,3-Dimethyl-8-phenylxanthine Selective A1 adenosine receptor antagonist Adenosine 88.5

F 7927 FSCPX Irreversible A1 adenosine receptor antagonist Adenosine 88.9M 6316 MRS 1754 Potent A2B adenosine receptor antagonist Adenosine 89.0

Table S2Viral RNAi Knockdown and Rational Drug Screening Reveals Survivin as a Therapeutic Target Reety Arora, Masahiro Shuda, Anna Guastafierro, Huichen Feng, Tuna Toptan, Yanis Tolstov, Daniel Normolle, Laura L. Vollmer,Andreas Vogt, Alexander Dömling, Jeffrey L. Brodsky, Yuan Chang* and Patrick S Moore*

LOPAC1280 Library Screen Results

A-0245 -N-Methyl carboxamidoadenosine

Adenosine receptor agonist with selectivity for A2 over A1 Adenosine 90.0

A-003 1,3-Diethyl-8-phenylxanthine A1 Adenosine receptor antagonist Adenosine 90.1

M-225 Metrifudil Adenosine receptor agonist which displays some selectivity for the A2 receptor type Adenosine 90.2

P-1012-Phenylaminoadenosine

Selective A2 adenosine receptor agonist; potent vasodilator; weak inhibitor of adenosine uptake by rat cerebral cortical synaptosomes

Adenosine 92.5

861669 S-(4-Nitrobenzyl)-6-thioguanosine Potent adenosine transport inhibitor Adenosine 93.3

D-108 1,3-Dipropyl-7-methylxanthine

Caffeine analog with some selectivity for A2 adenosine receptors Adenosine 93.4

C-101 8-Cyclopentyl-1,3-dipropylxanthine Selective A1 adenosine receptor antagonist Adenosine 94.6

M 1809 MRS 1523 Selective A3 adenosine receptor antagonist in rat Adenosine 94.9

C 9901N6-Cyclohexyladenosine

Selective A1 adenosine receptor agonist Adenosine 95.2

A-242 Alloxazine Selective A2b adenosine receptor antagonist Adenosine 97.0

A-022 1,3-Dipropyl-8-p-sulfophenylxanthine

Adenosine receptor antagonist with slight selectivity for A1 over A2 Adenosine 99.0

C-277 Chloro-IB-MECA A3 adenosine receptor agonist Adenosine 99.5

M 5501 N6-Methyladenosine

Adenosine analog useful for an adenosine reference standard since it is a poor substrate for adenosine deaminase

Adenosine 100.6

T 1633 Theophylline Selective A1 adenosine receptor antagonist. Adenosine 100.7

X-103 Xanthine amine congener A1 Adenosine receptor antagonist Adenosine 101.3

D 5385 1,7-Dimethylxanthine

Adenosine receptor ligand; major metabolite of caffeine Adenosine 102.9

B-152N6-Benzyl-5 -N-ethylcarboxamidoadenosine


E-114

erythro-9-(2-Hydroxy-3-nonyl)adenine hydrochloride

Potent adenosine deaminase inhibitor Adenosine 104.0

T 4500 Theobromine Weak adenosine receptor antagonist; weak phosphodiesterase Adenosine 104.1

V 5888 VUF 5574 Potent, selective and competitive A3 adenosine receptor antagonist Adenosine 104.9

H 8034 HE-NECA A2 Adenosine receptor agonist Adenosine 105.6

P 5679 3-n-Propylxanthine Weak competitive antagonist at both A1 and A2 adenosine receptors Adenosine 105.7

A-1451-Allyl-3,7-dimethyl-8-p-sulfophenylxanthine

Weak A2 adenosine receptor antagonist; water soluble Adenosine 106.0

C-141 CGS-21680 hydrochloride A2a adenosine receptor agonist. Adenosine 106.4

C 8031N6-Cyclopentyladenosine


C 60425 -(N-Cyclopropyl)carboxamidoadenosine

Potent A2 adenosine receptor agonist Adenosine 107.8

C-102 8-Cyclopentyl-1,3-dimethylxanthine Selective A1 adenosine receptor antagonist Adenosine 108.3

D-134 3,7-Dimethyl-I-propargylxanthine A2 adenosine receptor antagonist. Adenosine 109.5

E-111 (S)-ENBA Selective A1 adenosine receptor agonist Adenosine 109.7

N 2255 S-(4-Nitrobenzyl)-6-thioinosine Potent adenosine uptake inhibitor Adenosine 110.0

D 9766 Dipyridamole Coronary vasodilator; adenosine transport inhibitor Adenosine 110.3

P-108 N6-Phenyladenosine Potent A1 adenosine receptor agonist Adenosine 111.2

I-146 IB-MECA Selective A3 adenosine receptor agonist Adenosine 111.9

P 4532R(-)-N6-(2-Phenylisopropyl)adenosine

A1 Adenosine receptor agonist Adenosine 113.1

N-154 N6-Cyclopentyl-9-methyladenine Selective A1 adenosine receptor antagonist Adenosine 113.2

C-199 CGS-15943 Highly potent, non-selective A1 adenosine receptor antagonist Adenosine 114.3

A 9251 Adenosine Endogenous neurotransmitter and neuromodulator Adenosine 114.5

P-107N6-2-Phenylethyladenosine


D 5294 Dilazep hydrochloride Adenosine uptake inhibitor Adenosine 117.4

E 23875 -N-Ethylcarboxamidoadenosine

Potent adenosine receptor agonist with Adenosine 118.0

P 9689 Propentofylline Nerve growth factor stimulator; adenosine transport inhibitor; non-selective adenosine receptor antagonist Adenosine 119.7

A-236 AB-MECA High affinity A3 adenosine receptor agonist Adenosine 120.4

A 1755 Aminophylline ethylenediamine

A1/A2 adenosine receptor antagonist; diuretic; cardiac stimulant; smooth muscle relaxant Adenosine 121.6

C 0750 Caffeine Phosphodiesterase inhibitor; central stimulant Adenosine 127.1

E 1896 Etazolate hydrochloride Phosphodiesterase inhibitor Adenosine 131.5

A-202N6-2-(4-Aminophenyl)ethyladenosine

Potent, non-selective A3 adenosine receptor agonist Adenosine 133.6

P-152 S(-)-Pindolol 5-HT1A Serotonin receptor agonist Adrenergic 94.4I 3639 Isotharine mesylate beta-Adrenoceptor agonist; bronchodilator Adrenoceptor 78.1

N 5504 Naphazoline hydrochloride

alpha-Adrenoceptor agonist; imidazoline receptor agonist; vasoconstrictor Adrenoceptor 80.4

I-114 p-Iodoclonidine hydrochloride High affinity alpha2 adrenoceptor agonist Adrenoceptor 81.5

D 9815 Doxazosin mesylate alpha1 adrenoceptor blocker Adrenoceptor 81.6

I 8005 S(+)-Isoproterenol (+)-bitartrate

Sympathomimetic amine acting almost exclusively on beta adrenoceptors; bronchodilator; less active enantiomer of Isoproterenol

Adrenoceptor 82.3

B-003 Chloroethylclonidine dihydrochloride Irreversible alpha1B-adrenoceptor alkylating agent Adrenoceptor 85.6

N 7261 Nortriptyline hydrochloride Tricyclic antidepressant Adrenoceptor 86.2

U-104 UK 14,304 alpha2 Adrenoceptor agonist Adrenoceptor 87.6

R 0758 Ritodrine hydrochloride

beta2-Adrenoceptor agonist; relaxes uterine muscle contractions Adrenoceptor 90.1

T 4680 Terazosin hydrochloride alpha1-Adrenoceptor antagonist Adrenoceptor 90.7

D 0411 WB-4101 hydrochloride alpha1A Adrenoceptor antagonist Adrenoceptor 92.8

A 0779 p-Aminoclonidine hydrochloride alpha2 Adrenoceptor agonist Adrenoceptor 92.9

I 6504 (-)-Isoproterenol hydrochloride beta-Adrenoceptor agonist; increases cytosolic cAMP Adrenoceptor 93.6

D 5290(-)-alpha-Methylnorepinephrine

Active enantiomer; adrenoceptor agonist; vasoconstrictor; antihypertensive Adrenoceptor 94.3

I 5627 (±)-Isoproterenol hydrochloride

Sympathomimetic amine acting almost exclusively on beta adrenoceptors; bronchodilator Adrenoceptor 94.6

M 5154 Moxisylyte hydrochloride alpha1-Adrenoceptor antagonist Adrenoceptor 94.8

N-158 Naftopidil dihydrochloride alpha1 Adrenoceptor antagonist; antihypertensive Adrenoceptor 95.0

H 8759 MHPG sulfate potassium Norepinephrine metabolite Adrenoceptor 95.0

O 2378 Oxymetazoline hydrochloride

Partial alpha2A adrenoceptor agonist; agonist at serotonin 5-HT1A, 5-HT1B and 5-HT1D receptors and a mixed agonist-antagonist at 5-HT2C receptors

Adrenoceptor 95.0

I 2760 R(-)-Isoproterenol (+)-bitartrate

Sympathomimetic amine acting almost exclusively on beta adrenoceptors; bronchodilator; active enantiomer of Isoproterenol

Adrenoceptor 95.5

A 8404 Amitriptyline hydrochloride Tricyclic antidepressant Adrenoceptor 96.3

C 8417 DSP-4 hydrochloride

Adrenergic neurotoxin which induces acute and relatively selective degeneration of both central and peripheral noradrenergic terminals in the rat and mouse

Adrenoceptor 96.8

M 6524 Methoxamine hydrochloride alpha1 Adrenoceptor agonist Adrenoceptor 97.0

P 0778 Pindolol Nonselective beta adrenoceptor antagonist; vasodilator Adrenoceptor 97.1

B 5683 Betaxolol hydrochloride Selective beta1 adrenoceptor antagonist Adrenoceptor 97.3

E 4375 (-)-Epinephrine bitartrate Endogenous hormone and neurotransmitter Adrenoceptor 97.4

T 2528 Terbutaline hemisulfate beta-Adrenoceptor agonist; bronchodilator Adrenoceptor 97.6

F 6145 Fenspiride hydrochloride alpha-Adrenoceptor antagonist; NSAID Adrenoceptor 98.5

M 1559 Moxonidine hydrochloride

Selective alpha2A adrenoreceptor agonist; imidazoline binding site agonist; antihypertensive Adrenoceptor 99.0

P 9708 (S)-(-)-propafenone hydrochloride

beta-Adrenoceptor blocker; class 1C antiarrythmic agent Adrenoceptor 99.3

S 8260 Salbutamol beta2-Adrenoceptor agonist Adrenoceptor 99.4A 6351 A-315456 Selective alpha 1D-adrenoceptor antagonist Adrenoceptor 99.5

S 0278 (±)-Sotalol hydrochloride

Potent beta-adrenoceptor antagonist, a class III antiarrythmic; prolongs the action potential and increases the refractory period

Adrenoceptor 99.7

X 1251 Xylazine hydrochloride alpha2 Adrenoceptor agonist; anesthetic Adrenoceptor 100.6

T 4264 Tetrahydrozoline hydrochloride

alpha-Adrenoceptor agonist; imidazoline binding site ligand; vasoconstrictor Adrenoceptor 100.6

I 9531 Imiloxan hydrochloride Selective alpha2B-adrenoceptor antagonist Adrenoceptor 101.0

B 8406 Bretylium tosylate Adrenergic neuron blocking agent; antiarrhythmic; sympathomimetic Adrenoceptor 101.1

D 4526 Doxepin hydrochloride Antidepressant; antipruritic Adrenoceptor 101.3

D 0676 Dobutamine hydrochloride beta1 Adrenoceptor agonist Adrenoceptor 101.8

B-019 Phenoxybenzamine hydrochloride

Selective alpha adrenoceptor blocking agent; calmodulin antagonist Adrenoceptor 101.8

T 6394 S(-)-Timolol maleate beta Adrenoceptor antagonist; antihypertensive; antiarrhythmic; antiglaucoma agent Adrenoceptor 102.3

A-142 R(+)-Atenolol beta1 adrenoceptor antagonist; less active enantiomer Adrenoceptor 102.6

N 7127(±)-Normetanephrine hydrochloride

Norepinephrine metabolite Adrenoceptor 102.6

C-125 (±)-CGP-12177A hydrochloride Mixed beta adrenoceptor agonist/antagonist Adrenoceptor 102.7

Y 3125 Yohimbine hydrochloride

alpha2 Adrenoceptor antagonist isolated from Cortnanthe johimbe Adrenoceptor 103.3

B-016 Benoxathian hydrochloride Selective alpha1 adrenoceptor antagonist Adrenoceptor 103.5

N-153 Nylidrin hydrochloride beta Adrenoceptor agonist; peripheral vasodilator Adrenoceptor 103.8

N-151 Nisoxetine hydrochloride Potent and selective norepinephrine reuptake blocker Adrenoceptor 104.0

M 5391 (±)-Metoprolol (+)-tartrate Beta1-Adrenoceptor antagonist Adrenoceptor 104.4

M 2398 Metaproterenol hemisulfate beta2-Adrenoceptor agonist Adrenoceptor 104.4

E 3250 (-)-Ephedrine hemisulfate Adrenergic stimulant Adrenoceptor 105.1

A 7655 (±)-Atenolol Selective beta1 adrenoceptor antagonist; Adrenoceptor 105.3

F 4303 Fiduxosin hydrochloride alpha1-Adrenoceptor antagonist Adrenoceptor 105.4

R-104 Rauwolscine hydrochloride alpha2 Adrenoceptor antagonist Adrenoceptor 105.5

P 7791 Prazosin hydrochloride Peripheral alpha1 adrenoceptor antagonist Adrenoceptor 105.6

I-127 ICI 118,551 hydrochloride Highly selective beta2 adrenoceptor antagonist Adrenoceptor 106.8

A 0937 (±)-Norepinephrine (+)bitartrate Adrenergic neurotransmitter Adrenoceptor 107.0

A 9512 L(-)-Norepinephrine bitartrate Adrenergic neurotransmitter; vasoconstrictor Adrenoceptor 107.4

F 9552 Formoterol beta2-Adrenoceptor agonist Adrenoceptor 107.5L 3040 L-765,314 Potent, selective alpha-1B adrenoceptor antagonist. Adrenoceptor 108.5

H 2380 6-Hydroxy-DL-DOPA

Precursor of the catecholaminergic neurotoxin, 6-hydroxydopamine; converted to 6-hydroxydopamine by L-aromatic amino acid decarboxylase

Adrenoceptor 108.6

M 7065 MK-912 Selective alpha2A adrenoreceptor agonist Adrenoceptor 108.7

M 9651 Maprotiline hydrochloride Selective norepinephrine reuptake inhibitor Adrenoceptor 108.8

H 1377 MHPG piperazine Norepinephrine metabolite Adrenoceptor 109.1

S 5068 Salmeterol xinafoate beta2 Adrenoceptor agonist Adrenoceptor 109.4

P 0884 (±)-Propranolol hydrochloride

beta Adrenoceptor antagonist; cardiac depressant (anti-arrhythmic) Adrenoceptor 110.1

G-110 Guanabenz acetate Centrally acting alpha2 adrenoceptor agonist; antihypertensive Adrenoceptor 110.1

B-161 B-HT 933 dihydrochloride Selective alpha2 adrenoceptor agonist Adrenoceptor 110.4

E 4642 (±)-Epinephrine hydrochloride Adrenoceptor agonist Adrenoceptor 110.5

F 1016 Fenoterol hydrobromide Beta2-adrenoceptor agonist; bronchodilator Adrenoceptor 110.8

D 7815 R(-)-Denopamine beta1-adrenoceptor agonist Adrenoceptor 112.8B-169 BRL 37344 sodium Selective beta3 adrenoceptor agonist Adrenoceptor 113.2

B-015 Bromoacetyl alprenolol menthane Alkylating beta adrenoceptor antagonist Adrenoceptor 113.9

A 8423 Amiodarone hydrochloride

alpha and beta adrenoceptor agonist; inhibits binding of 1,4-dihydropyridine to L-type Ca2+ channels; coronary vasodilator

Adrenoceptor 114.2

S 1563 SKF 86466 Potent and selective alpha2 adrenoceptor antagonist Adrenoceptor 114.2

O 0250 (±)-Octopamine hydrochloride Neurotransmitter Adrenoceptor 114.3

R 9525 RX 821002 hydrochloride Selective alpha2-adrenoceptor antagonist Adrenoceptor 114.4

B-0126-Fluoronorepinephrine hydrochloride

alpha Adrenoceptor agonist Adrenoceptor 114.4

T 6050 Tulobuterol hydrochloride

beta-Adrenoceptor agonist related to structurally to terbutaline; bronchodilator Adrenoceptor 114.4

L 1011 Labetalol hydrochloride Competitive beta-adrenoceptor antagonist Adrenoceptor 114.6

H 0131 (±)-Vanillylmandelic acid Metabolite of epinephrine Adrenoceptor 114.7

P 7561 Phentolamine mesylate

ATP-sensitive K+ channel blocker; alpha adrenoceptor antagonist Adrenoceptor 115.1

X 3253 Xamoterol hemifumarate Specific beta1-Adrenoceptor specific partial agonist Adrenoceptor 115.2

C-223 Cirazoline hydrochloride

Selective alpha1 adrenoceptor agonist; non-selective imidazoline binding site ligand Adrenoceptor 115.3

U-101 Urapidil, 5-Methyl- Selective alpha1A adrenoceptor antagonist; antihypertensive Adrenoceptor 115.4

C 5976 CL 316,243 Beta3 adrenoceptor agonist; anti-obesity agent Adrenoceptor 115.7S 0752 (±)-Synephrine alpha-Adrenoceptor agonist; vasoconstrictor Adrenoceptor 115.8

D 3900 Desipramine hydrochloride Antidepressant Adrenoceptor 116.9

P 8688 (S)-Propranolol hydrochloride

Active beta-adrenoceptor receptor blocking enantiomer; 5-HT1 serotonin receptor antagonist Adrenoceptor 117.2

P 8813 Protriptyline hydrochloride Norepinephrine reuptake blocker Adrenoceptor 117.2

A 8676 Alprenolol hydrochloride beta Adrenoceptor antagonist Adrenoceptor 117.4

A-143 S(-)-Atenolol beta1 adrenoceptor antagonist Adrenoceptor 117.5

P 6126 Phenylephrine hydrochloride alpha1 Adrenoceptor agonist; mydriatic; decongestant Adrenoceptor 117.9

U-100 Urapidil hydrochloride

alpha1 Adrenoceptor antagonist and 5-HT1A serotonin receptor partial agonist; antihypertensive Adrenoceptor 118.3

X 6000 Xylometazoline hydrochloride

alpha-Adrenoceptor agonist; imidazoline binding site ligand Adrenoceptor 119.3

S 8688 SR 59230A oxalate beta3-Adrenoceptor antagonist Adrenoceptor 119.8

G 1043 Guanfacine hydrochloride alpha2-Adrenoceptor agonist Adrenoceptor 120.0

C-231 CGP 20712A methanesulfonate Selective beta1-adrenoceptor antagonist Adrenoceptor 121.9

A-129 Amoxapine Tricyclic antidepressant; inhibits neuronal uptake of norepinephrine Adrenoceptor 122.3

C 7897 Clonidine hydrochloride alpha2 Adrenoceptor agonist; antihypertensive Adrenoceptor 123.1

T 7947 Tomoxetine Norepinephrine reuptake blocker Adrenoceptor 124.4

S 5013 Albuterol hemisulfate beta Adrenoceptor agonist Adrenoceptor 129.8

P-119 (±)-Pindobind Analog of pinolol which contains a bromo-acetyl group capable of alkylation of beta-adrenoceptors

Adrenoceptors 26.4

D-193DL-alpha-Difluoromethylornithine hydrochloride

Selective irreversible ornithine decarboxylase (ODC) inhibitor. Angiogenesis 83.2

N 3510 Niclosamide Protonophoric anthelmintic; uncouples oxidative phosphorylation Antibiotic 29.2

D 6140 Demeclocycline hydrochloride

Tetracycline antibiotic; interferes with protein synthesis Antibiotic 87.7

C 8645 Cinoxacin Quinolone antibacterial; enzyme inhibitor Antibiotic 90.1

P 5396 Phosphomycin disodium Antibiotic; interferes with cell wall synthesis Antibiotic 92.8

P 4668 Praziquantel Ca2+ Ionophore; anthelmintic Antibiotic 93.2

T 9567 Thiolactomycin Inhibits bacterial, not eukaryotic, myristate synthesis. Effective as antitrypanosomal and antimalarial. Antibiotic 95.7

C 8145 Cefsulodin sodium salt hydrate

Third generation cephalosporin antibiotic; interferes with cell wall synthesis Antibiotic 97.0

V 8138

Vancomycin hydrochloride from Streptomyces orientalis

Amphoteric glycopeptide antibiotic; interefers with cell wall syntehsis by bind to peptidoglycan Antibiotic 97.3

D 9891 Doxycycline hydrochloride

6-deoxytetracycline antibiotic; interferes with protein synthesis Antibiotic 97.6

C 8270 Cephapirin sodium Cephalosporin C antibiotic; interferes with cell wall synthesis Antibiotic 97.9

O 8757 Ofloxacin Fluorinated quinolone antibacterial; interferes with DNA synthesis Antibiotic 99.5

N 4382 Nalidixic acid sodium Inhibits bacterial DNA polymerase (DNA gyrase) Antibiotic 100.5

C 6048 Cefmetazole sodium Semi-synthetic antibiotic derived from cephamycin C; interferes with cell wall synthesis Antibiotic 100.6

P 7136 Pyrazinecarboxamide Antibiotic; tuberculostatic Antibiotic 102.1

A 1784 Aminopterin Dihydrofolate reductase inhibitor Antibiotic 102.7O 0877 Oxolinic acid Quinolone antibacterial; DNA gyrase inhibitor Antibiotic 103.7

C 8395 Cephradine Semisynthetic cephalosporin antibiotic; interferes with cell wall synthesis Antibiotic 104.0

C 4895 Cephalexin hydrate Semi-synthetic cephalosporin antibiotic; interferes with cell wall synthesis Antibiotic 105.0

C 6895 Cefaclor Semi-synthetic cephalosporin antibiotic; interferes with cell wall synthesis Antibiotic 109.1

L 2906 Lomefloxacin hydrochloride DNA gyrase inhibitor Antibiotic 111.3

P 9297 Paromomycin sulfate

Oligosacchiride-type antibiotic; interferes with protein synthesis Antibiotic 111.4

C 5020 Cefazolin sodium Semi-synthetic antibiotic; interferes with cell wall synthesis Antibiotic 112.6

M 2537 Mevastatin Antibiotic; inhibits post-translational prenylation of proteins such as Ras and geranylgeranylation of Rho Antibiotic 112.6

C 7912 Cefotaxime sodium Broad spectrum third generation cephalosporin antibiotic; interferes with cell wall synthesis Antibiotic 113.9

C 4520 Cephalothin sodium Semi-synthetic cephalosporin antibiotic; interferes with cell wall synthesis Antibiotic 115.8

C 5793 Ceftriaxone sodium Third generation cephalosporin antibiotic; interferes with cell wall synthesis Antibiotic 116.1

T 7883 Trimethoprim Potent inhibitor of bacterial and protozoal dihydrofolate reductase Antibiotic 118.2

C 3270 Cephalosporin C zinc salt Antibiotic; interferes with cell wall synthesis Antibiotic 122.3

F 6426 Foliosidine Anticonvulsant; prevents cardiac arrhythmia caused by electric stimulation of the atria or by aconitine

Anticonvulsant 86.8

D 4505 Phenytoin sodium Anticonvulsant; anti-epileptic Anticonvulsant 88.5

P 4543 Valproic acid sodium Anticonvulsant Anticonvulsant 89.5

D 4007 5,5-Diphenylhydantoin

Anticonvulsant; appears to stabilize excitable membranes perhaps through effects on Na+, K+, and Ca2+ channels

Anticonvulsant 93.9

E 7138 Ethosuximide Inhibits voltage-gated sodium channels; used for the treatment of absence-type seizures

Anticonvulsant 94.6

L 3791 Lamotrigine Anticonvulsant Anticonvulsant 97.7

A 9345N-(4-Amino-2-chlorophenyl)phthalimide

Potent anticonvulsant Anticonvulsant 102.7

P 7295 Primidone Anticonvulsant Anticonvulsant 105.4

D 7814 Dubinidine Anticonvulsant Anticonvulsant 106.7

Z 2001 Zonisamide sodiumAntiepileptic; effective in various animal epilepsy models and in humans with both partial and generalized epileptic seizures

Anticonvulsant 109.6

G-154 Gabapentin Anticonvulsant that may modulate certain types of Ca2+ channel currents; analgesic

Anticonvulsant 116.9

C 4024 Carbamazepine Analgesic; anticonvulsant Anticonvulsant 122.7

C 9911 (S)-(+)-Camptothecin DNA topoisomerase I inhibitor Apoptosis 17.2

E 1383 Etoposide Topoisomerase II inhibitor; induces apoptosis; cell cycle inhibitor Apoptosis 21.7

L 2037 beta-Lapachone Induces apoptosis in HL-60 cells; anticancer agent Apoptosis 51.5R 2625 Retinoic acid Induces caspase-dependent apoptosis Apoptosis 53.2

E 2375Emetine dihydrochloride hydrate

Apoptosis inducer; RNA-Protein translation inhibitor Apoptosis 73.5

X 3628 XK469 Topoisomerase II beta inhibitor; apoptosis inducer. Apoptosis 87.6

B 2009 Benzamide Inhibitor of Poly(ADP-ribose) synthetase which is activated by nitric oxide; neuroprotective agent Apoptosis 103.6

I-138 1,5-Isoquinolinediol Potent inhibitor of Poly(ADP-ribose) synthetase which is activated by nitric oxide; neuroprotective agent Apoptosis 105.5

A 1895 Aurintricarboxylic acid DNA topoisomerase II inhibitor Apoptosis 108.5

A 0966 4-Amino-1,8-naphthalimide Poly(ADP-ribose) polymerase (PARP) inhibitor Apoptosis 110.2

I 9890m-Iodobenzylguanidine hemisulfate

Antitumor agent which inhibits ADP ribosylation; induces changes in the mitochondrial membrane potential, activation of caspase-3 and DNA fragmentation

Apoptosis 112.7

A 0788 3-aminobenzamide Poly(ADP-ribose) synthetase (PARS) inhibitor Apoptosis 120.7

F 6300 Flumazenil Benzodiazepine receptor antagonist Benzodiazepine 79.0

E-002Methyl beta-carboline-3-carboxylate

Benzodiazepine receptor inverse agonist Benzodiazepine 97.3

D 8555N,N-Dihexyl-2-(4-fluorophenyl)indole-3-acetamide

High affinity ligand for glial mitochondrial benzodiazepine receptors

Benzodiazepine 98.2

E-007

Methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate

Benzodiazepine receptor inverse agonist Benzodiazepine 109.0

Z 4900 Zopiclone Benzodiazepine receptor agonist Benzodiazepine 109.5

L 9787 L-655,708 Selective ligand for the benzodiazepine site of GABA-A receptors which contain the alpha5 subunit

Benzodiazepine 111.2

C 6862 CB34 High affinity ligand at peripheral benzodiazepine receptors

Benzodiazepine 124.8

M 2922

3-Methyl-6-(3-[trifluoromethyl]phenyl)-1,2,4-triazolo[4,3-b]pyridazine

Selective BZ1 benzodiazepine receptor agonist Benzodiazepine 105.0

I 1149 Iodoacetamide Alkylating reagent for cysteine and histidine residues in proteins; irreversible protein inhibitor Biochemistry 1.4

T 1132 Tetraethylthiuram disulfide Alcohol dehydrogenase inhibitor Biochemistry 3.7

C 9511 Z-L-Phe chloromethyl ketone Bovine chymotrypsin A-gamma inhibitor Biochemistry 37.8

A 0500 Acetamide Carbonic anhydrase inhibitor Biochemistry 71.8

L 8397L-Leucinethiol, oxidized dihydrochloride

Peptide inhibitor of aminopeptidases Biochemistry 75.5

C 59134-Chloromercuribenzoic acid

Carboxy- and aminopeptidase inhibitor Biochemistry 78.8

D 9305 1-Deoxynojirimycin hydrochloride alpha-glucosidase I-II inhibitor Biochemistry 85.0

M 1387 4-Methylpyrazole hydrochloride Alcohol dehydrogenase inhibitor Biochemistry 85.4

B 7283 Benserazide hydrochloride Peripheral decarboxylase inhibitor Biochemistry 88.9

A 6671 Actinonin Leucine aminopeptidase inhibitor Biochemistry 89.0

B 8385 Bestatin hydrochloride Aminopeptidase inhibitor Biochemistry 91.5

P 2742 PD 404,182 KDO-8-P synthase inhibitor Biochemistry 92.1

A 0760 L-azetidine-2-carboxylic acid Inhibits collagen synthesis Biochemistry 92.6

P 9375 1,10-Phenanthroline monohydrate

Metalloprotease inhibitor; chelates iron, zinc and other divalent metals Biochemistry 93.3

H 93823-Hydroxybenzylhydrazine dihydrochloride

Centrally acting aromatic amino acid decarboxylase inhibitor; penetrates the blood-brain barrier Biochemistry 94.7

C-007

10-(alpha-Diethylaminopropionyl)-phenothiazine hydrochloride

Selective butyrylcholinesterase inhibitor Biochemistry 97.8

D 7505 2,2 -Bipyridyl Metalloprotease inhibitor Biochemistry 97.9E 3132 E-64 Irreversible inhibitor of cysteine proteases Biochemistry 98.0

M 1777 N-Methyl-1-deoxynojirimycin

Interferes with metabolism of N-linked glycoproteins by inhibition of glucosidase Biochemistry 98.3

H 98824-Hydroxybenzhydrazide

Phenylalanine ammonia-lyase inhibitor; used to measure reducing sugar levels Biochemistry 98.6

C 4911 Chlorothiazide Carbonic anhydrase inhibitor; diuretic; antihypertensive Biochemistry 99.5

T 4376N-p-Tosyl-L-phenylalanine chloromethyl ketone

Blocks LPS- or cytokine-induced activation of nuclear factor kB (NFkB), which, blocks the induction of iNOS and COX-2 transcription; blocks activation of pp70s6k by all mitogens

Biochemistry 100.8

A 6011 Acetazolamide Carbonic anhydrase inhibitor; diuretic Biochemistry 101.3

E 3876 N-EthylmaleimideSulfhydryl alkylating agent that inactivates NADP-dependent isocitrate dehydrogenase and many endonucleases

Biochemistry 105.6

T 1505 Tetraisopropyl pyrophosphoramide Selective inhibitor of butyrylcholinesterase Biochemistry 107.6

F-124 Furafylline Cytochrome P4501A2 inhibitor Biochemistry 107.8

M-129 L-alpha-Methyl DOPA

L-aromatic amino acid decarboxylase inhibitor; antihypertensive Biochemistry 109.6

H 4759 Hydrochlorothiazide Carbonic anhydrase inhibitor; diuretic Biochemistry 109.8

A 71484-Aminobenzamidine dihydrochloride

Trypsin inhibitor; competitive kallikrein inhibitor Biochemistry 110.1

A 7762 L-allylglycine Glutamic acid decarboxylase inhibitor Biochemistry 110.6

C-203 2-Chloro-2-deoxy-D-glucose Analog of 2-fluoro-2-deoxyglucose Biochemistry 110.8

D 6518 Diethylenetriaminepentaacetic acid

Zinc-dependent proteases carboxypeptidase A and aminopeptidase N inhibitor; chelating agent Biochemistry 111.6

O 2751 Sodium Oxamate Competitive lactate dehydrogenase inhibitor Biochemistry 112.4

A 9657 (±)-p-Aminoglutethimide . Biochemistry 112.4

D 7910 3,4-Dichloroisocoumarin Serine protease inhibitor Biochemistry 112.6

B 3501 Betaine hydrochloride Product in choline-betaine osmoregulatory pathway Biochemistry 113.4

D 1262P1,P4-Di(adenosine-5 )tetraphosphate triammonium

Dinucleoside polyphosphate that competitively inhibits ADP-induced platelet aggregation Biochemistry 117.0

A 4508

O-(Carboxymethyl)hydroxylamine hemihydrochloride

Non-selective aminotransferase inhibitor Biochemistry 117.0

C-126 S-(-)-CarbidopaPeripherally active L-aromatic amino acid decarboxylase inhibitor; used in combination with levodopa for the treatment of Parkinson s Disease.

Biochemistry 118.0

E 4378

Ethylene glycol-bis(2-aminoethylether)-N,N,N ,N -tetraacetic acid

Carboxypeptidase B inhibitor; chelating agent useful for the determination of calcium in the presence of magnesium

Biochemistry 118.4

C 9033beta-Chloro-L-alanine hydrochloride

Alanine aminotransferase inhibitor Biochemistry 119.5

D 17912,4-Dinitrophenyl 2-fluoro-2-deoxy-beta-D-glucopyranoside

exo-beta-(1,3)-Glucanase inhibitor Biochemistry 119.8

E 0381 Epibestatin hydrochloride Metallo-protease inhibitor; aminopeptidase inhibitor Biochemistry 120.5

A 8456

4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride

Irreversible serine protease inhibitor Biochemistry 121.9

R 7385 Phosphoramidon disodium

Inhibitor of mammalian enkephalinase and some metallo-endopeptidases; potent inhibitor of thermolysin and other bacterial metallo-endopeptidases

Biochemistry 127.4

B 6506 Benzamidine hydrochloride Peptidase inhibitor Biochemistry 129.1

S 7809 SKF 96365 Selective inhibitor of receptor-mediated and voltage-gated Ca2+ entry Ca2+ Channel 56.1

N 0287 NNC 55-0396 Selective T-type calcium channel inhibitor. Ca2+ Channel 70.5

D 2521 Diltiazem hydrochloride

Ca2+ channel antagonist selective for slow, or L-type, channels; stimulates 1,4-dihydropyridine binding to Ca2+ channels; coronary vasodilator

Ca2+ Channel 94.6

M 5441 Mibefradil dihydrochloride T-type Ca2+ channel blocker Ca2+ Channel 96.1

N-144 Nitrendipine Ca2+ channel blocker; antihypertensive Ca2+ Channel 98.1

N 7634 Nifedipine L-type Ca2+ channel blocker; vasodilator Ca2+ Channel 98.2

N 7510 Nicardipine hydrochloride L-type Ca2+ channel antagonist; antihypertensive Ca2+ Channel 98.3

V 4629 (±)-Verapamil hydrochloride

L-type Ca2+ channel modulator; adrenoceptor antagonist; antiarryhthmic; cardiac depressant; coronary vasodilator

Ca2+ Channel 98.8

Y-101 YS-035 hydrochloride L-type Ca2+ channel blocker; verapamil derivative Ca2+ Channel 100.7

M 5644(±)-Methoxyverapamil hydrochloride

L-type Ca2+ channel antagonist Ca2+ Channel 102.0

F-131 FPL 64176 Potent L-type Ca2+ channel activator Ca2+ Channel 103.2

C 5270 Cinnarizine Ca2+ channel blocker; central and peripheral vasodilator Ca2+ Channel 104.9

M 1692 MRS 1845 Store-operated calcium (SOC) channel inhibitor. Ca2+ Channel 105.8

P 7912 Phloretin Blocks L-type Ca2+ channels Ca2+ Channel 108.2

N-149 Nimodipine Potent L-type Ca2+ channel antagonist Ca2+ Channel 113.6

B-112 (±)-Bay K 8644 L-type Ca2+ channel agonist Ca2+ Channel 116.1

B 5016 Bepridil hydrochloride

Non-selective Ca2+ channel blocker which stimulates the binding of 1,4-dihydropyridine-based drugs to Ca2+ channels; anti-anginal

Ca2+ Channel 116.3

F 9677 Felodipine L-type calcium channel blocker Ca2+ Channel 128.3

S 3317 SKF 94836 Phosphodiesterase III (PDE III) inhibitor. Calcium Signaling 95.1

W-102 ( R)-(+)-WIN 55,212-2 mesylate High affinity cannabinoid receptor agonist Cannabinoid 90.8

P 0359 Palmitoylethanolamide Endogenous CB2 cannabinoid receptor agonist Cannabinoid 92.9

C 1112 CP55940 Cannabinoid receptor agonist Cannabinoid 105.8

A 1977 N-arachidonylglycine

Arachidonyl amino acid which inhibits pain; inhibits the hydrolytic activity of fatty acid amide hydrolase (FAAH) on anandamide

Cannabinoid 108.5

J 4252 JWH-015 Selective CB2 cannabinoid receptor agonist Cannabinoid 110.4

I-151 Indomethacin morpholinylamide CB2 cannabinoid receptor ligand Cannabinoid 102.7

B 5681 Bay 11-7085 Inhibits cytokine induced IkB (Inhibitor of NFkB) phosphorylation Cell Cycle 3.8

E 3380 Ellipticine Cytochrome P450 (CYP1A1)and DNA topoisomerase II inhibitor Cell Cycle 5.9

C 8221 Caffeic acid phenethyl ester NFkB inhibitor Cell Cycle 40.4

C 9510 Pyrocatechol Carcinogen; causes DNA strand breakage Cell Cycle 83.4A 3145 Apigenin Arrests cell cycle at G2/M phase Cell Cycle 87.8

M 6680Se-(methyl)selenocysteine hydrochloride

Potent chemopreventive agent Cell Cycle 89.2

D 7802 DaidzeinIsoflavonoid cytostatic agent that arrests the cell cycle at G1; inhibitor of mitochondrial aldehyde dehydrogenase

Cell Cycle 90.8

M 6690 MDL 28170 Cell permeable calpain I and II inhibitor Cell Cycle 93.3

H 7779 Retinoic acid p-hydroxyanilide

Vitamin A acid analog with antiproliferative activity in cultured human breast cancer cells Cell Cycle 99.3

T 5575 TG003 Potent, specific, and reversible Cdc2-like kinase (Clk) inhibitor. Competes with ATP. Cell Cycle 101.7

F 6627 5-Fluorouracil Thymidylate synthetase inhibitor; leads to accumulation of cells in S phase Cell Cycle 102.8

M 9511 Minocycline hydrochloride

Basement membrane protease inhibitor; inhibits endothelial cell proliferation and angiogenesis. Cell Cycle 103.5

G 2536 Ganciclovir

Pro-drug nucleoside analog; upon thymidine kinase expression,converted to a phosphorylated active analog and incorporated into DNA, causing death of the malignant dividing cell

Cell Cycle 105.6

R 9644 RibavirinAntiviral agent; its metabolite, ribavirin 5 -phosphate, is an inhibitor of inosine monophosphate (IMP) dehydrogenase

Cell Cycle 109.1

F 0881 Fusidic acid sodium Inhibits protein synthesis in prokaryotes Cell Cycle 114.8R 8875 Rotenone Inhibitor of mitochondrial electron transport Cell Stress 36.3

U 6007 U-83836 dihydrochloride Free radical lipid peroxidation inhibitor Cell Stress 49.5

D 3648N,N,N ,N -Tetramethylazodicarboxamide

Thiol-oxidizing agent Cell Stress 82.5

N 5636 3-Nitropropionic acid

Mitochondrial inhibitor; excitotoxin shown to cause brain lesions similar to those of Huntington s disease Cell Stress 84.3

D 5439 2,3-Dimethoxy-1,4-naphthoquinone

Redox cycling agent used to study role of ROS (reactive oxygen species) Cell Stress 86.8

T 4512 (±)-Taxifolin Flavonoid, antioxidant Cell Stress 91.2

C 1251 (+)-Catechin Hydrate Antioxidant; free radical scavenger Cell Stress 95.5

M 4008 Morin Flavonoid with anti-oxidant properties; oxyradical scavenger Cell Stress 96.0

I 7388 Isoxanthopterin Product of xanthine oxidase oxidation of pterin, an enzyme involved in reactive oxygen formation. Cell Stress 99.0

A 9335 Astaxanthin Potent antioxidant Cell Stress 101.5

T 5625 (±)-alpha-Lipoic AcidCoenzyme needed for the activity of enzyme complexes such as those of pyruvate dehydrogenase and glycine decarboxylase

Cell Stress 101.8

U 5882 U-74389G maleate Free radical lipid peroxidation inhibitor Cell Stress 102.0

L 4900 Lonidamine

Inhibits the energy metabolism of neoplastic cells by interfering with mitochondrial hexokinase, cellular respiration, and glycolysis; damages cell and mitochondrial membranes

Cell Stress 102.1

C 2321 Carcinine dihydrochloride Antioxidant; hydroxy radical scavanger Cell Stress 106.9

H 1384 Hypotaurine Antioxidant that binds hydroxyl radicals; GABA transport inhibitor Cell Stress 107.5

D 5766 5,5-Dimethyl-1-pyrroline-N-oxide Neuroprotective agent Cell Stress 109.1

A 8003 Allopurinol Xanthine oxidase inhibitor; inhibits the final step in uric acid biosynthesis Cell Stress 115.9

A 5922 AmifostineRadioprotective agent; selectively protects normal tissues from the damaging effects of anti-neoplastic radiation therapy

Cell Stress 124.7

C 0625 Caffeic Acid Antioxidant; inhibits the synthesis of leukotrienes that are involved in immunoregulation and inflammation Cell Stress 130.0

M-001 Proglumide Selective cholecystokinin receptor antagonist Cholecystokinin 94.6

I 9778 CR 2945 Selective gastrin/CCK(B) receptor antagonist Cholecystokinin 100.0

L-109 Lorglumide sodium Potent and selective non-peptide cholecystokinin (CCK) receptor antagonist; orally active

Cholecystokinin 113.3

N 7906

2-(alpha-Naphthoyl)ethyltrimethylammonium iodide

Selective, fluorescent inhibitor of choline acetyltransferase Cholinergic 20.5

M 3184 MG 624Nicotinic acetylcholine receptor antagonist; selectively inhibits alpha-bungarotoxin sensitive receptors that contain the alpha7 subunit

Cholinergic 38.7

E-100 (-)-Eseroline fumarate

Metabolite of physostigmine (eserine); potent analgesic; cholinesterase inhibitor Cholinergic 72.9

T 6692

N,N,N-trimethyl-1-(4-trans-stilbenoxy)-2-propylammonium iodide

Nicotinic acetylcholine receptor antagonist Cholinergic 78.6

P 3520 Pentolinium di[L(+)-tartrate]

Peripheral ganglionic nicotinic acetylcholine receptor antagonist Cholinergic 79.5

A 6883 Atropine methyl bromide

Competitive muscarinic acetylcholine receptor antagonist Cholinergic 82.9

T-122 Telenzepine dihydrochloride

Selective M1 muscarinic acetylcholine receptor antagonist and anti-ulcer agent Cholinergic 85.2

H 9002 L-Hyoscyamine Competitive antagonist at post-ganglionic synapses and on smooth muscle Cholinergic 86.7

V-100 (±)-Vesamicol hydrochloride Potent inhibitor of vesicular acetylcholine storage Cholinergic 87.2

O 2881 Oxybutynin Chloride Muscarinic acetylcholine receptor antagonist Cholinergic 87.5

D 1260 Decamethonium dibromide

Nicotinic acetylcholine receptor partial agonist; depolarizing neuromuscular blocker Cholinergic 90.5

A 9013 BW 284c51 Selective acetylcholinesterase inhibitor Cholinergic 91.0

G 8134 Gallamine triethiodide

M2 muscarinic acetylcholine receptor antagonist; muscle relaxant Cholinergic 91.1

L-134 Linopirdine Stimulates release of acetylcholine and other neurotransmitters; cognitive enhancer Cholinergic 91.1

C 4382 Carbachol Acetylcholine receptor agonist Cholinergic 91.7

N 2001 Neostigmine bromide Reversible inhibitor of acetylcholinesterase Cholinergic 92.0

H-108 Hemicholinium-3 Potent and selective choline uptake blocker Cholinergic 92.1

N 5260(-)-Nicotine hydrogen tartrate salt

Prototype nicotinic acetylcholine receptor agonist Cholinergic 92.8

A 2251Acetyl-beta-methylcholine chloride

M1 muscarinic acetylcholine receptor agonist Cholinergic 93.7

W 4761 WB 64 Ligand for the allosteric site of the M2 muscarinic acetylcholine receptor. Cholinergic 94.3

I 8898 IvermectinPositive allosteric modulator of alpha7 neuronal nicotinic acetylcholine receptor; also modulates glutamate-GABA-activated chloride channels

Cholinergic 94.4

E 8375 (-)-Physostigmine Cholinesterase inhibitor Cholinergic 95.3

S 7882 (-)-Scopolamine,n-Butyl-, bromide Cholinergic receptor antagonist Cholinergic 98.2

K 4262 Karakoline Nicotinic acetylcholine receptor antagonist Cholinergic 98.3

P 1918 Pancuronium bromide

Aminosteroidal neuromuscular blocking agent; skeletal muscle relaxant Cholinergic 98.9

C 5259 Bethanechol chloride

Muscarinic acetylcholine receptor agonist; resistant to acetylcholinesterase and non-specific cholinesterases Cholinergic 98.9

M 9020 Mecamylamine hydrochloride Nicotinic acetylcholine receptor antagonist Cholinergic 100.1

M-140 Methylcarbamylcholine chloride Selective nicotinic acetylcholine receptor agonist Cholinergic 100.4

P 6628 Pilocarpine nitrate Nonselective muscarinic acetylcholine receptor agonist Cholinergic 100.4

D-142

4-Diphenylacetoxy-N-(2-chloroethyl)piperidine hydrochloride

Irreversible muscarinic acetylcholine receptor antagonist Cholinergic 100.7

P 8891 Propantheline bromide

Muscarinic acetylcholine receptor antagonist; antispasmodic Cholinergic 100.8

S 8502 (-)-Scopolamine methyl bromide


B 8262 Benztropine mesylate Muscarinic acetylcholine receptor antagonist Cholinergic 101.4

T 9778 Tropicamide M4 muscarinic acetylcholine receptor antagonist Cholinergic 101.8

C-008 (+)-cis-Dioxolane iodide High affinity muscarinic acetylcholine receptor agonist Cholinergic 102.0

D 7909 Dicyclomine hydrochloride


E 3256 Edrophonium chloride Acetylcholinesterase inhibitor Cholinergic 103.1

P 5114 Pempidine tartrate A neuronal nicotinic acetylcholine receptor antagonist; potent ganglioblocker; Antihypertensive Cholinergic 103.7

D-104 4-DAMP methiodide M3 muscarinic acetylcholine receptor antagonist. Cholinergic 103.8

T 2265 Tetraethylammonium chloride

Nicotinic acetylcholine receptor antagonist; K+ channel blocker Cholinergic 104.2

T 1516 Trihexyphenidyl hydrochloride

Muscarinic acetylcholine receptor antagonist; centrally acting anticholinergic Cholinergic 104.5

P 7412 Pirenzepine dihydrochloride

Selective M1 muscarinic acetylcholine receptor antagonist Cholinergic 105.6

M-105 Methoctramine tetrahydrochloride

Selective M2 muscarinic acetylcholine receptor antagonist Cholinergic 106.3

O-100 Oxotremorine methiodide

Nonselective muscarinic acetylcholine receptor agonist Cholinergic 106.3

O 9126 Oxotremorine sesquifumarate salt

Muscarinic acetylcholine receptor agonist with preference for the M2 receptor Cholinergic 106.8

C 7041 McN-A-343 M1 muscarinic acetylcholine receptor agonist. Cholinergic 107.0

H 3146 Hydroxytacrine maleate Cholinesterase inhibitor Cholinergic 107.1

I 1637 Ipratropium bromide Muscarinic acetylcholine receptor antagonist; bronchodilator Cholinergic 107.3

D 58911,1-Dimethyl-4-phenyl-piperazinium iodide

Nicotinic acetylcholine receptor agonist Cholinergic 107.9

D 7938 DBO-83 Nicotinic acetylcholine receptor agonist Cholinergic 108.5

A 37739-Amino-1,2,3,4-tetrahydroacridine hydrochloride

Cholinesterase inhibitor; reported to be useful Cholinergic 108.8

P 6503 (+)-Pilocarpine hydrochloride Cholinergic receptor agonist Cholinergic 109.4

O 3752 Orphenadrine hydrochloride

Muscarinic acetylcholine receptor antagonist; H1 histamine receptor antagonist Cholinergic 109.7

C 1754 Choline bromide Choline acetyltransferase substrate Cholinergic 110.7

A-140Arecaidine propargyl ester hydrobromide

Potent muscarinic acetylcholine receptor agonist exhibiting a slight selectivity for M2 receptors Cholinergic 110.9

L 4376 alpha-Lobeline hydrochloride Neuronal nicotinic acetylcholine receptor agonist Cholinergic 111.0

D126608 Propofol Short acting general anesthetic Cholinergic 111.2

A 6134 Arecoline hydrobromide Acetylcholine receptor agonist Cholinergic 112.3

A 5626 Acetylthiocholine chloride

Nicotinic acetylcholine receptor agonist; acetylcholinesterase substrate Cholinergic 112.5

B-121 Bromoacetylcholine bromide

Affinity alkylating agent of nicotinic acetylcholine receptors Cholinergic 113.1

H 2138 Hexamethonium dichloride Nicotinic acetylcholine receptor antagonist Cholinergic 114.2

N 9765 (+)-Nicotine (+)-di-p-toluoyl tartrate

Less active enantiomer of naturally-occurring (-)-nicotine Cholinergic 114.3

H-127

Hexahydro-sila-difenidol hydrochloride, p-fluoro analog

High affinity muscarinic acetylcholine receptor antagonist, but displays altered selectivity (M3 > M1 > M2)

Cholinergic 115.1

D-149Dihydro-beta-erythroidine hydrobromide

Competitive nicotinic acetylcholine receptor antagonist. Cholinergic 116.1

A-138 Aminobenztropine High affinity muscarinic acetylcholine receptor ligand Cholinergic 116.2

S 2250 (-)-Scopolamine methyl nitrate


H 0879 Hexamethonium bromide

Blocks nicotinic acetylcholine receptors at autonomic ganglia Cholinergic 117.7

S 1875 (-)-Scopolamine hydrobromide

Cholinergic receptor antagonist; isolated from members of the Solanaceae family Cholinergic 118.2

C-011 OXA-22 iodide Potent muscarinic acetylcholine receptor agonist Cholinergic 119.4

H 0126 DL-Homatropine hydrobromide Muscarinic acetylcholine receptor antagonist Cholinergic 120.5

P 9797 Pyridostigmine bromide Cholinesterase inhibitor Cholinergic 120.5

M-104 (±)-Muscarine chloride Muscarinic acetylcholine receptor agonist Cholinergic 121.6

C 5923 (-)-Cotinine Major metabolite of nicotine in humans Cholinergic 126.4

B 3650 Betaine aldehyde chloride

Intermediate in choline-betaine osmoregulatory pathway; product of choline dehydrogenation Cholinergic 127.4

S 8251 Succinylcholine chloride Nicotinic acetylcholine receptor antagonist. Cholinergic 135.5

A 0257 Atropine sulfate Muscarinic acetylcholine receptor antagonist Cholinergic 136.5

A 0382 Atropine methyl nitrate Muscarinic acetylcholine receptor antagonist Cholinergic 143.8

N 47795-Nitro-2-(3-phenylpropylamino)benzoic acid

Potent Cl- channel blocker Cl- Channel 115.0

144509 N-Phenylanthranilic acid Cl- channel blocker Cl- Channel 124.8

I-117 R(+)-IAA-94 Potent Cl- channel inhibitor Cl- Channel 139.8

P 3510 Papaverine hydrochloride Phosphodiesterase inhibitor Cyclic

Nucleotides 80.7

I 3766 Isoliquiritigenin Soluble guanylyl cyclase activator and aldose reductase inhibitor

Cyclic Nucleotides 81.1

M 4659 Milrinone Phosphodiesterase III inhibitor Cyclic Nucleotides 87.4

P 8293 Protoporphyrin IX disodium Activates soluble guanylyl cyclase Cyclic

Nucleotides 88.5

Y-102 YC-1 NO-independent guanylyl cyclase activator Cyclic Nucleotides 91.9

F 6886 Forskolin Activates adenylate cyclase; antihypertensive and vasodilator; isolated from Coleus forskohlii


B 7880 8-Bromo-cAMP sodium Membrane-permeable analog of cAMP Cyclic

Nucleotides 95.3

Q 0125 Quercetin dihydrate Mitochondrial ATPase and phosphodiesterase (PDE) inhibitor; inhibits PI3-K activity


T 2057 Trequinsin hydrochloride Phosphodiesterase III (PDE III) inhibitor Cyclic

Nucleotides 97.1

S-153 SQ 22536 Adenylyl cyclase inhibitor Cyclic Nucleotides 98.8

T 7254Na-p-Tosyl-L-lysine chloromethyl ketone hydrochloride

Adenylyl cyclase inhibitor; blocks the LPS- or cytokine-induced activation of nuclear factor kB (NFkB)


N-211 NS 2028 Specific soluble guanylyl cyclase inhibitor Cyclic Nucleotides 101.5

O 3636 ODQ Potent and selective NO-sensitive guanylyl cyclase inhibitor


B 8279 Ro 20-1724 Potent and selective cAMP phosphodiesterase inhibitor


T 7692 T-1032 Potent and specific inhibitor of phosphodiesterase V (PDE V)


P 1784 Pentoxifylline Inhibits synthesis of tumor necrosis factor alpha (TNF-alpha); phosphodiesterase inhibitor


E 1279 Enoximone Selective phosphodiesterase III (PDE III) inhibitor Cyclic Nucleotides 106.4

Q 3504 Quazinone Phosphodiesterase III (PDE III) inhibitor Cyclic Nucleotides 107.5

T 8067 T-0156 Potent phosphodiesterase V (PDE V) inhibitor Cyclic Nucleotides 107.8

I 0782 Imazodan Selective phosphodiesterase II (PDEII) inhibitor Cyclic Nucleotides 109.9

Z 3003 Zardaverine Phosphodiesterase III (PDE III) and phosphodiesterase IV (PDE IV) inhibitor


C 0737 Cilostazol Specific type III phosphodiesterase (PDE) inhibitor Cyclic Nucleotides 112.2

R 6520 Rolipram Selective cAMP-dependent phosphodiesterase (Type IV) cAMP-dependent inhibitor


V 6383 Vinpocetine Ca2+ /calmodulin-dependent phosphodiesterase1 (PDE1) inhibitor.


C 39128-(4-Chlorophenylthio)-cAMP sodium

Membrane-permeable analog of cAMP Cyclic Nucleotides 116.0

Z 0878 Zaprinast Selective cGMP-phosphodiesterase type V inhibitor Cyclic Nucleotides 117.0

M 25478-Methoxymethyl-3-isobutyl-1-methylxanthine

Selective inhibitor of Ca2+-calmodulin-dependent phosphodiesterase (PDE I)


B 1381 8-Bromo-cGMP sodium Membrane-permeable analog of cGMP Cyclic

Nucleotides 120.3

C 7971 Cilostamide cGMP-inhibited phosphodieserase inhibitor (PDE III) Cyclic Nucleotides 128.1

C 4479 9-cyclopentyladenine

Cell-permeable, non-competitive adenylyl cyclase inhibitor; targets the P-site domain


I 0157 Ibudilast Phosphodiesterase IV (PDE IV) inhibitor Cyclic Nucleotides 151.9

C 7238 CV-3988

Competitive platelet activating factor (PAF) receptor antagonist. Inhibits PAF-induced human platelet aggregation and bronchoconstriction in the guinea pig.

Cytokines & Growth Factors

113.4

B 7651Brefeldin A from Penicillium brefeldianum

Fungal metabolite that disrupts the structure and function of the Golgi apparatus

Cytoskeleton and ECM 22.3

V 8879 Vincristine sulfate Inhibitor of microtubule assembly Cytoskeleton and ECM 41.1

P 4405 Podophyllotoxin Antineoplastic glucoside; inhibitor of microtubule assembly


C 9754 Colchicine Prevents tubulin polymerization Cytoskeleton and ECM 46.8

V 1377 Vinblastine sulfate salt Inhibitor of microtubule assembly Cytoskeleton

and ECM 48.2

T 7402 Taxol Antitumor agent; promotes assembly of microtubules and inhibits tubulin disassembly process


T-144 (±)-Thalidomide Selective inhibitor of the biosynthesis of tumor necrosis factor a (TNF-alpha); angiogenesis inhibitor


M 1404 Nocodazole Disrupts microtubules by binding to beta-tubulin Cytoskeleton and ECM 82.3

D 3634 2,3-Butanedione Reversible myosin ATPase inhibitor Cytoskeleton and ECM 104.9

D 4434 Clodronic acid Matrix metalloproteinase 1 (MMP1) and collagenase inhibitor


C 0253 Chlorambucil DNA crosslinker; induces apoptosis DNA 89.9

N 8659 Nimustine hydrochloride

Antineoplastic; bifunctional nitrosourea alkylating anticancer agent DNA 92.9

P 4394 CisplatinInduces intrastrand DNA crosslinks; effects are regulated by kinases, phosphatases and Ca2+/calmodulin

DNA 97.1

P 6909 Phosphonoacetic acid DNA Polymerase inhibitor DNA 101.5

C 0400 Carmustine DNA alkylating agent; causes interstrand crosslinks DNA 108.1

C 2235 CB 1954 Prodrug activated by NAD(P)H quinone oxidoreductase-2 DNA 116.8

C 6628 Chloroquine diphosphate

Antimalarial; anti-amoebic; anti-inflammatory; binds strongly to double-stranded DNA DNA 117.3

C 0768 Cyclophosphamide monohydrate Cancer chemotherapeutic; cross-links DNA DNA 122.0

C 2538 Carboplatin Antineoplastic, Alkylating Agent DNA 139.4

M 2011 Melphalan Antineoplastic; forms DNA intrastrand crosslinks by bifunctional alkylation in 5 -GGC sequences

DNA Metabolism 41.3

M 6545 Mitoxantrone DNA synthesis inhibitor DNA Metabolism 43.0

I 1656 Idarubicin Antineoplastic DNA Metabolism 49.8

C 6645Cytosine-1-beta-D-arabinofuranoside hydrochloride

Selective inhibitor of DNA synthesis DNA Metabolism 65.9

A 2385 5-azacytidine DNA methyltransferase inhibitor DNA Metabolism 72.0

A 9898 (-)Amethopterin Inactive isomer of amethopretin, a folic acid antagonist

DNA Metabolism 84.8

A 8598 Ancitabine hydrochloride Antineoplastic DNA

Metabolism 86.2

A 6770 Methotrexate Folic acid antagonist DNA Metabolism 87.2

H 8627 Hydroxyurea Antineoplastic; inactivates ribonucleoside reductase which blocks the synthesis of deoxynucleotides

DNA Metabolism 91.5

F 8791 5-fluoro-5 -deoxyuridine DNA synthesis inhibitor; antiproliferative DNA

Metabolism 94.3

A 8723 Altretamine Antineoplastic, Alkylating Agent DNA Metabolism 94.9

M 3047 MizoribineArrests at G/S; inhibits de novo synthesis of nucleotides by inhibition of inosine monophosphate dehydrogenase

DNA Metabolism 110.0

B 5002 5-Bromo-2 -deoxyuridine

Thymidine analog; incorporated into DNA during S-phase of cell cycle


246379 Azelaic acidAntiproliferative on melonama cells; inhibits mitochondrial oxidoreductases of the respiratory chain and inhibits DNA synthesis


A 9809 Amsacrine hydrochloride DNA topoisomerase II inhibitor DNA Repair 7.0

B 1266 p-BenzoquinoneBenzene metabolite; induces mutations in DNA at G:C base pairs; induces writhing in mice; topoisomerase II inhibitor

DNA Repair 100.4

B 2292 O6-benzylguanine Irreversible inhibitor of the mammalian DNA repair protein, O6-alkylguanine-DNA alkyltransferase DNA Repair 108.0

A 4393Apomorphine hydrochloride hemihydrate

Non-selective dopamine receptor agonist Dopamine 42.3

P-1063-Phenylpropargylamine hydrochloride

Potent, time-dependent inhibitor of dopamine beta-hydroxylase (DBH) Dopamine 44.5

D-027R(-)-Propylnorapomorphine hydrochloride

Highly potent and selective D2 dopamine receptor agonist Dopamine 52.2

S 3066 SKF 89626 D1 dopamine receptor agonist Dopamine 61.3

L-133 L-750,667 trihydrochloride Selective D4 dopamine receptor antagonist Dopamine 73.2

L 8401 LE 300 Potent, selective D1 dopamine receptor antagonist Dopamine 73.8

D-042R(-)-N-Allylnorapomorphine hydrobromide

Dopamine receptor agonist Dopamine 74.9

H 8502 Dopamine hydrochloride Endogenous neurotransmitter Dopamine 75.2

I-119 Indatraline hydrochloride

Potent inhibitor of dopamine, norepinephrine and serotonin reuptake Dopamine 77.8

N-140

N-(p-Isothiocyanatophenethyl)spiperone hydrochloride

Selective irreversible D2 dopamine receptor antagonist Dopamine 78.1

L-106 Loxapine succinate Dibenzoxazepine antipsychotic agent Dopamine 79.0

D 5814 Dihydrexidine hydrochloride D1 dopamine receptor agonist Dopamine 79.3

T 0780 Thiothixene hydrochloride Dopamine receptor antagonist; antipsychotic Dopamine 80.3

T 0410 Tiapride hydrochloride

D2 and D3 dopamine receptor antagonist; antipsychotic Dopamine 80.5

M 2776 Methylergonovine maleate

Dopamine antagonist; ergot alkaloid which interacts with serotonergic, dopaminergic and alpha-adrenergic systems

Dopamine 82.0

D-029R(-)-2,10,11-Trihydroxyaporphine hybrobromide

D2 dopamine receptor agonist Dopamine 82.2

P 1793 Pimozide Ca2+ channel antagonist; antipsychotic; D2 dopamine receptor antagonist Dopamine 84.6

P 6656 Promazine hydrochloride

D2 dopamine receptor antagonist; phenothiazine antipsychotic Dopamine 86.0

L-135 L-741,626 Selective D2 dopamine receptor antagonist Dopamine 87.6

H 12524-Hydroxy-3-methoxyphenylacetic acid

Dopamine metabolite Dopamine 87.6

D-155 Dihydroergocristine methanesulfonate

Ergot alkaloid; vasoconstrictor; partial agonist at dopaminergic receptors and adrenoceptors; antagonist at serotonergic receptors

Dopamine 87.6

M 42513-Methoxy-4-hydroxyphenethylamine hydrochloride

Major metabolite of L-DOPA; reference standard for chromatographic analysis Dopamine 87.8

S 3191 SKF 83565 hydrobromide

Atypical D1 dopamine receptor agonist; displays antagonist activity in vitro and agonist activity in vivo Dopamine 88.0

C-130 (±)-Chloro-APB hydrobromide D1 dopamine receptor agonist. Dopamine 88.2

M 0763 Metoclopramide hydrochloride

5-HT3 Serotonin receptor antagonist; D2 dopamine receptor antagonist; anti-emetic Dopamine 89.9

G 9659 GBR-12935 dihydrochloride Dopamine reuptake inhibitor Dopamine 90.6

J-102 JL-18 Clozapine analog which is 25 fold selective for the D4 dopamine receptor versus the D2 dopamine receptor Dopamine 91.3

A-255 A-77636 hydrochloride Potent, orally active D1 dopamine receptor agonist Dopamine 91.9

T-165 R(+)-Terguride Ergot derivative; dehydrogenated analog of Lisuride; partial dopamine receptor agonist. Dopamine 92.5

D-030

R(-)-2,10,11-Trihydroxy-N-propylnoraporphine hydrobromide

Potent and selective D2 dopamine receptor agonist Dopamine 92.6

P 4015 1-Phenyl-3-(2-thiazolyl)-2-thiourea Dopamine beta-hydroxylase inhibitor Dopamine 94.4

C-2074 -Chloro-3-alpha-(diphenylmethoxy)tropane hydrochloride

Dopamine reuptake blocker. Dopamine 94.8

F 4765 Fluphenazine dihydrochloride Dopamine receptor antagonist; antipsychotic Dopamine 95.1

H 1512 Haloperidol Dopamine receptor antagonist; antipsychotic Dopamine 95.2

H 68921-(4-Hydroxybenzyl)imidazole-2-thiol

Dopamine beta-hydroxylase inhibitor Dopamine 95.4

B 9308 BP 897 Partially selective D3 dopamine receptor agonist Dopamine 96.0S 8010 (±)-Sulpiride D2 Dopamine receptor antagonist; antipsychotic Dopamine 96.2



Q-111 (±)-Quinpirole dihydrochloride

Selective D2-like dopamine receptor agonist which possesses some activity at D3 dopamine receptors Dopamine 96.4

P 6402 Perphenazine D2 dopamine receptor antagonist; sigma receptor agonist; phenothiazine antipsychotic Dopamine 96.7

D-003 R(-)-Apocodeine hydrochloride Dopamine receptor agonist; apomorphine metabolite Dopamine 97.0

L-131 L-745,870 hydrochloride Selective D4 dopamine receptor antagonist Dopamine 97.8

P 0618 cis-(±)-8-OH-PBZI hydrobromide D3 dopamine receptor agonist Dopamine 97.9

F 6513 Fusaric acid Dopamine beta-hydroxylase inhibitor; antibiotic isolated from the fungus Fusarium heterosporium Dopamine 98.7

D-033 (+)-Butaclamol hydrochloride Dopamine receptor antagonist Dopamine 99.0

D-122 Domperidone Peripheral dopamine receptor antagonist that does not cross the blood-brain barrier; anti-emetic Dopamine 99.1

B-135 R(+)-6-Bromo-APB hydrobromide D1 Dopamine receptor agonist Dopamine 99.3

D 5886 N-Methyldopamine hydrochloride Dopamine receptor agonist Dopamine 99.3

H-168 R-(+)-7-Hydroxy-DPAT hydrobromide

Selective D3 dopamine receptor agonist; active enantiomer of (±)-7-hydroxy-DPAT Dopamine 99.4

P 7780 Propionylpromazine hydrochloride


C 8138 Chlorpromazine hydrochloride

Dopamine receptor antagonist; anti-emetic; antipsychotic Dopamine 99.7

T 28794-Hydroxyphenethylamine hydrochloride

Dopamine receptor agonist Dopamine 100.1

F 6800 Fenoldopam bromide Peripheral D1 dopamine receptor agonist Dopamine 101.5

P 9178 Prochlorperazine dimaleate

Antipsychotic agent; used in the treatment of spastic gastrointestinal disorders Dopamine 101.5

H 31324-Methoxy-3-hydroxyphenethylamine hydrochloride

Dopamine metabolite Dopamine 101.7

B-138 BTCP hydrochloride Selective blocker of dopamine reuptake Dopamine 101.9

T 2896 Triflupromazine hydrochloride


E-101 S-(-)-Eticlopride hydrochloride

Potent and selective D2 dopamine receptor antagonist Dopamine 102.7

T 9025 Thioridazine hydrochloride

Dopamine receptor antagonist; Ca2+ channel antagonist; antipsychotic Dopamine 103.2

D-054 R(+)-SCH-23390 hydrochloride Selective D1 dopamine receptor antagonist Dopamine 103.5

S 7771 (-)-Sulpiride D2 dopamine receptor antagonist; antipsychotic Dopamine 103.8

F-114 cis-(Z)-Flupenthixol dihydrochloride Dopamine receptor antagonist; antipsychotic Dopamine 104.4

A 1260 Amantadine hydrochloride

Dopamine releaser used in the treatment of Parkinsonism and drug- Dopamine 104.6

G-120 GYKI 52895 Selective dopamine reuptake inhibitor; antiparkinsonian; antidepressant Dopamine 104.8

D 9628L-3,4-Dihydroxyphenylalanine

Precursor to dopamine; antiparkinsonian agent Dopamine 105.1

R 4152 Ropinirole hydrochloride Selective D2 dopamine receptor agonist Dopamine 105.1

S 7395 Spiperone hydrochloride Selective D2 dopamine receptor antagonist. Dopamine 105.3

S-168 (±)-SKF 38393, N-allyl-, hydrobromide D1 dopamine receptor agonist. Dopamine 105.3

I-139 S(-)-IBZM D2 dopamine receptor ligand Dopamine 105.6



F-100 Fluspirilene Dopamine receptor antagonist; antipsychotic Dopamine 106.0

D-206 S(-)-DS 121 hydrochloride

Dopamine autoreceptor antagonist with some selectivity for the D3 dopamine receptor binding site Dopamine 106.4

P-233 PD 168,077 maleate Selective D4 dopamine receptor agonist Dopamine 107.0

U-116 U-99194A maleate D3 dopamine receptor antagonist Dopamine 107.1

P-102 R(+)-3PPP hydrochloride

Binds with high selectivity to sigma receptors, yet has no affinity for phencyclidine receptors; dopamine receptor agonist

Dopamine 107.3

B 2134 (+)-Bromocriptine methanesulfonate

D2 dopamine receptor agonist; inhibits prolaction secretion Dopamine 107.7

R-121 S(+)-Raclopride L-tartrate Selective D2 dopamine receptor antagonist Dopamine 108.0

S 1441 Cortexolone maleate D2 dopamine receptor antagonist Dopamine 108.4

D 1507

L-3,4-Dihydroxyphenylalanine methyl ester hydrochloride

Precursor to L-DOPA that crosses the blood-brain barrier Dopamine 108.9

A 8762 N-Acetyldopamine monohydrate Dopamine analog possessing antitumor activity Dopamine 109.6

P-103 S(-)-3PPP hydrochloride

Dopamine autoreceptor agonist; postsynaptic dopamine receptor antagonist Dopamine 110.1

P 9233 Piribedil maleate Non-selective dopamine receptor agonist Dopamine 110.3

L-118 R(+)-Lisuride hydrogen maleate

D2 Dopamine receptor agonist; serotonin mixed receptor agonist/antagonist; inhibitor of prolactin secretion; used clinically for both prolactin inhibition and migraine

Dopamine 110.3

C 1671 Chlorprothixene hydrochloride

D2 dopamine receptor antagonist; blocks a subset of GABA-A receptors in rat cortex that is also blocked by clozapine

Dopamine 110.4

L-122 S-(-)-LisurideD2 Dopamine receptor agonist; alpha- and beta-adrenoceptor antagonist; D1 dopamine receptor antagonist

Dopamine 110.9

C 7230

N-(2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl)-3-methoxybenzamide

Selective D4 dopamine receptor agonist Dopamine 111.1

H 8653 (±)-7-Hydroxy-DPAT hydrobromide Selective D3 dopamine receptor agonist Dopamine 111.4

P-216 (±)-PD 128,907 hydrochloride Selective D3 dopamine receptor agonist Dopamine 111.4

T 8516 Trifluoperazine dihydrochloride

Calmodulin antagonist; dopamine receptor antagonist; antipsychotic; sedative Dopamine 111.7

S-159 R(-)-SCH-12679 maleate D1 dopamine receptor antagonist; antipsychotic Dopamine 112.4

S-143 (±)-6-Chloro-PB hydrobromide D1 dopamine receptor agonist Dopamine 112.9

R-118 Risperidone D2 Dopamine receptor antagonist; 5-HT2 serotonin receptor antagonist; antipsychotic Dopamine 112.9

M-153 Mesulergine hydrochloride

Dopaminergic receptor agonist exhibiting antiparkinsonian activity; 5-HT2C serotonin receptor antagonist

Dopamine 113.1

B-102 Bupropion hydrochloride Selective dopamine reuptake inhibitor; antidepressant Dopamine 113.5

Q-110 Quinelorane dihydrochloride

D2 Dopamine receptor agonist; 2-aminopyridine analog of Quinpirole Dopamine 113.6

D 1414 Droperidol D1, D2 dopamine receptor antagonist Dopamine 113.7

O-111 (±)-Octoclothepin maleate

D2 Dopamine receptor antagonist; serotonin receptor antagonist Dopamine 114.0

P-105 (±)-PPHT hydrochloride Potent D2 dopamine receptor agonist Dopamine 114.3

D-002 6,7-ADTN hydrobromide Dopamine receptor agonist Dopamine 115.6

D-044 Amfonelic acidIncreases dopamine release during electrical stimulation; appears to mobilize dopamine release from storage compartments

Dopamine 116.6

E-140 Ergocristine Ergot alkaloid Dopamine 116.7U-115 U-101958 maleate Selective D4 dopamine receptor antagonist Dopamine 116.8

D-047 (±)-SKF-38393 hydrochloride D1 Dopamine receptor agonist Dopamine 117.9

D-052 GBR-12909 dihydrochloride Selective dopamine reuptake inhibitor Dopamine 118.9

N 1530 Nomifensine maleate Dopamine reuptake inhibitor; antidepressant Dopamine 120.1

P 8828 Pergolide methanesulfonate Dopamine receptor agonist; antiparkinsonian Dopamine 121.2

B-168 (±)-Butaclamol hydrochloride

Dopamine receptor antagonist; selective for D2 over D1 Dopamine 121.3

P-183 S(+)-PD 128,907 hydrochloride Selective D3 dopamine receptor agonist Dopamine 121.4

Q-102 (-)-Quinpirole hydrochloride

Selective D2-like dopamine receptor agonist with some selectivity for D3 sites Dopamine 121.4

D-031 Dipropyldopamine hydrobromide Dopamine receptor agonist Dopamine 121.8

T-103 Trifluperidol hydrochloride Dopamine receptor antagonist; antipsychotic Dopamine 124.7

D 91283,4-Dihydroxyphenylacetic acid

Product of dopamine degradation by MAO and aldehyde dehydrogenase Dopamine 127.0

C 6305 Clozapine Atypical neuroleptic agent which display greater affinity for the D4 dopamine receptors over D2 or D3 Dopamine 128.2

A-206 Agroclavine Dopamine receptor agonist; ergot alkaloid Dopamine 130.6

F 8175 Farnesylthiosalicylic acid Non-toxic Ras inhibitor G protein 77.9

P 7083 (-)-Perillic acidInterferes with activity of p21ras and other small G proteins by inhibiting post-translational cysteine isoprenylation

G protein 100.8

S 4063 SCH-202676 hydrobromide

Allosteric agonist and antagonist of G protein coupled receptors (GPCRs) G protein 107.9

N 4784 NF449 octasodium salt Potent G protein antagonist, selective for Gs-alpha G protein 126.7

T-200 TPMPA Selective GABA-C receptor antagonist GABA 74.2

A 2129 GABA Endogenous neurotransmitter GABA 86.3

P 1675 Picrotoxin GABA-C receptor antagonist; powerful, nonspecific CNS stimulant isolated from Anamirta cocculin GABA 89.8

G-002 Isoguvacine hydrochloride GABA-A receptor agonist GABA 90.4

B 5399 (±)-Baclofen GABA-B receptor agonist; antispastic agent; muscle relaxant GABA 92.1

C 0987 CGP-13501 Positive allosteric modulator of GABA-B receptors GABA 93.0

A 41473-Amino-1-propanesulfonic acid sodium

GABA-A receptor agonist GABA 93.7

A 3539 Gabaculine hydrochloride

GABA transaminase inhibitor; conformationally constrained GABA analog GABA 93.9

N 4034 NCS-356 gamma-Hydroxybutyrate receptor agonist GABA 94.2

P 20163-alpha,21-Dihydroxy-5-alpha-pregnan-20-one

Positive allosteric modulator of GABA-A receptors GABA 94.5

N 4159 NCS-382 gamma-Hydroxybutyrate receptor antagonist GABA 94.9

H 8645 (+)-HydrastinePotent competitive GABA-A receptor antagonist which is more potent than bicuculline; isolated from Corydalis stricta

GABA 95.8

A 71623-Aminopropylphosphonic acid

GABA-B receptor agonist GABA 96.9

T-101 THIP hydrochloride GABA-A receptor agonist, with some GABA-C receptor agonist activity GABA 97.5

D 5297Dehydroisoandrosterone 3-sulfate sodium

Negative allosteric modulator of GABA-A receptors GABA 98.5

G-019 Muscimol hydrobromide GABA-A receptor agonist, water soluble GABA 99.2

N-142 NO-711 hydrochloride Potent and selective GABA uptake inhibitor. GABA 99.3

B-103(-)-Bicuculline methbromide, 1(S), 9(R)

GABA-A receptor antagonist GABA 99.9

S 7936 SB 205384 GABA-A receptor modulator selective for the alpha3beta2gamma2 subunit combination GABA 101.1

G-007 Guvacine hydrochloride GABA uptake inhibitor GABA 101.9

P 8887 5alpha-Pregnan-3alpha-ol-20-one

Positive allosteric modulator of GABA-A chloride channels GABA 103.0

V 8261 (±)-gamma-Vinyl GABA

Selective GABA transaminase (GABA-T) inhibitor; anticonvulsant GABA 103.5

T 1694 (E)-4-amino-2-butenoic acid Potent GABA-C receptor agonist. GABA 105.9

P-162 Pregnenolone sulfate sodium

Neurosteroid that antagonizes the GABA-A receptor chloride channels GABA 106.3

E-006N-Methyl-beta-carboline-3-carboxamide

GABA-A receptor antagonist GABA 107.0

P 9159 Piperidine-4-sulphonic acid

Potent and specific agonist for GABA postsynaptic receptor sites GABA 110.7

S 9066 SKF 89976A hydrochloride

GABA transporter type 1 (GAT-1) inhibitor that crosses the blood brain barrier GABA 111.3

I18008 Isonipecotic acid GABA-A receptor agonist GABA 112.8C 0862 CGP-7930 Positive allosteric modulator of GABA-B receptors GABA 114.0

P 50525alpha-Pregnan-3alpha-ol-11,20-dione

Neurosteroid that acts as a positive allosteric modulator of the GABA-A receptor; anesthetic GABA 116.7

194336 5-Aminovaleric acid hydrochloride Weak GABA-B receptor antagonist GABA 117.9

A 6566 2-Hydroxysaclofen GABA-B receptor antagonist GABA 119.9P-118 Phaclofen GABA-B receptor antagonist GABA 120.7

T-112 Tracazolate Non-benzodiazepine anxiolytic which has a high differential between sedative and anxiolytic doses GABA 122.4

A-230 gamma-Acetylinic GABA GABA transaminase (GABA-T) inhibitor GABA 122.6

I 0375 Imidazole-4-acetic acid hydrochloride Competitive antagonist at GABA-C receptors GABA 123.3

211672 (±)-Nipecotic acid GABA uptake inhibitor GABA 124.6

S-106 SR-95531Specific GABA-A receptor antagonist; does not affect GABA-transaminase or glutamate-decarboxylase activities.

GABA 127.0

A-201 cis-4-Aminocrotonic acid GABA-C receptor agonist GABA 132.4

C 0424 PK 11195 Peripheral benzodiazepine receptor antagonist GABA 132.7

A-196 SKF 97541 hydrochloride

Selective GABA-B receptor agonist; GABA-C receptor antagonist GABA 135.6

S 4692 Sobuzoxane DNA topoisomerase II inhibitor; induces apoptosis. Gene Regulation 96.2

S 2501 Spermidine trihydrochloride

Binds to the polyamine modulatory site of the NMDA glutamate receptor Glutamate 24.5

S 9186 SIB 1757 Highly selective mGlu5 metabotropic glutamate receptor antagonist Glutamate 72.2

K 0250 Kainic acidExcitatory amino acid receptor agonist selective for the kainate glutamate receptor subtype; conformationally restricted analog of L-glutamic acid

Glutamate 73.0

E 2031 EliprodilNR2B selective NMDA receptor antagonist (polyamine site); potential clinical use to treat both acute and chronic pain.

Glutamate 80.0

A 9950 Aniracetam Increases ion conductance through AMPA glutamate receptors; reported to display Glutamate 83.9

D 0540 DNQX Potent, competitive kainate/quisqualate glutamate receptor antagonist Glutamate 85.4

C 9847 Cyclothiazide Blocks the rapid desensitization of AMPA glutamate receptors Glutamate 87.8

I 2892 Ifenprodil tartrate Blocks the polyamine binding site associated with the NMDA glutamate receptor; neuroprotective Glutamate 88.1

A 4910(±)-2-Amino-3-phosphonopropionic acid

NMDA glutamate receptor antagonist Glutamate 91.4

P 0547 Pentamidine isethionate

NMDA glutamate receptor antagonist; neuroprotective agent; antimicrobial agent prescribed for the treatment of AIDS-associated Pneumocystis carinii pneumonia

Glutamate 92.3

A 9699 (±)-HA-966 NMDA glutamate receptor antagonist which appears to act by competing with glycine Glutamate 94.2

D 1064 Dihydrokainic acid Non-transportable glutamate analog that blocks glutamate receptors Glutamate 94.5

C 3909 D-Cycloserine Excitatory amino acid; partial agonist at the glycine modulatory site of the NMDA glutamate receptor Glutamate 95.4

C-104 (±)-CPP Potent and selective NMDA glutamate receptor antagonist; anticonvulsant Glutamate 96.2

A-155 trans-(±)-ACPD Metabotropic glutamate receptor agonist Glutamate 97.0

D 8941

2,6-Difluoro-4-[2-(phenylsulfonylamino)ethylthio]phenoxyacetamide

Selective, high affinity AMPA ionotropic glutamate receptor agonist; reduces ischemia-induced performance deficits in rats.

Glutamate 97.1

P 1801 L-Glutamic acid, N-phthaloyl- Selective NMDA glutamate receptor agonist Glutamate 97.4

C-237(2S,1 S,2 S)-2-(carboxycyclopropyl)glycine

Potent group II metabotropic glutamate receptor agonist Glutamate 98.0

N 2034 CR 2249 Facilitates glycine action at NMDA glutamate receptors Glutamate 98.3

G-119 GYKI 52466 hydrochloride

Selective AMPA/kainate glutamate receptor antagonist; anticonvulsant; skeletal muscle relaxant Glutamate 98.3

M-108 (-)-MK-801 hydrogen maleate

Less active enantiomer of (+)-MK-801 hydrogen maleate; anticonvulsant; NMDA glutamate receptor antagonist.

Glutamate 98.3

C-271 CX 546 Positive AMPA glutamate receptor modulator; more potent than 1-BCP Glutamate 98.6

I 2765 (±)-Ibotenic acidPotent NMDA/metabotropic glutamate receptor agonist; excitotoxin; originally isolated from Amanita pantherina and Amanita muscaria

Glutamate 100.3

P 5295 Piracetam Prototypical nootropic; modulates Na+-flux at AMPA glutamate receptors Glutamate 100.4

D-1336,7-Dichloroquinoxaline-2,3-dione

High affinity antagonist specific for the strychnine-insensitive glycine binding site of the NMDA glutamate receptor

Glutamate 100.8

L 0258 L-701,324 Selective antagonist at the glycine site of the NMDA glutamate receptor Glutamate 100.8

S 9311 SIB 1893 Selective and noncompetitive antagonist of mGlu5 metabotropic glutamate receptor Glutamate 101.8

N 7904 NS 521 oxalate Benzimidazolone neuroprotective agent Glutamate 101.8

N-183 NBQX disodium Neuroprotective AMPA/kainate glutamate receptor antagonist; water soluble salt of NBQX Glutamate 102.8

Q 2128 (+)-Quisqualic acid Active enantiomer of quisqualic acid; Glutamate 102.8

F 8927 Flupirtine maleate NMDA glutamate receptor antagonist; centrally acting analgesic Glutamate 103.0

D 3689(S)-3,5-Dihydroxyphenylglycine

Group I metabotropic glutamate receptor (mGluR1) agonist Glutamate 103.6

M 3262 N-Methyl-D-aspartic acid NMDA glutamate receptor agonist Glutamate 103.8

G-017 (±)-AMPA hydrobromide

Potent excitatory amino acid that interacts selectively with central AMPA/kainate glutamate receptors Glutamate 103.9

A-244 trans-Azetidine-2,4-dicarboxylic acid

mGluR1 and mGluR5 metabotropic glutamate receptor agonist Glutamate 104.1

P63204 Quinolinic acid Neurotoxin which has neuroexcitatory activity; metabolite of trytophan Glutamate 104.1

D 2531Dextromethorphan hydrobromide monohydrate

Allosteric antagonist at NMDA-controlled ion channels Glutamate 104.3

A 1910(±)-2-Amino-4-phosphonobutyric acid


W-105 S(-)-Willardiine AMPA/kainate glutamate receptor agonist Glutamate 104.4

M-1873-Methoxy-morphanin hydrochloride

Metabolite of dextromethorphan Glutamate 105.2

M-216 MDL 105,519 High affinity NMDA glutamate receptor antagonist at the glycine site Glutamate 105.9

K 3375 Kynurenic acidExcitatory amino acid receptor antagonist; blocks kainic acid-induced neurotoxicity; metabolite of tryptophan

Glutamate 106.0

C-239 CNQX disodium Potent, competitive AMPA/kainate glutamate receptor antagonist Glutamate 106.4

A 7845 ATPO Competitive GluR1-4 (AMPA-preferring) glutamate receptor antagonist Glutamate 106.9

W-110 S-5-Iodowillardiine Potent AMPA glutamate receptor agonist. Glutamate 107.3

I 0154 IEM-1460 Selective inhibitor of a subtype of AMPA glutamate receptors (Ca2+ permeable, lacking GluR2 subunits) Glutamate 107.3

G-111gamma-D-Glutamylaminomethylsulfonic acid

Kainate/quisqualate glutamate receptor antagonist Glutamate 107.5

D 8816N-(3,3-Diphenylpropyl)glycinamide

NMDA glutamate receptor open channel blocker. Glutamate 108.1

M 54356-Methyl-2-(phenylethynyl)pyridine hydrochloride

Highly selective, non-competitive mGluR5 metabotropic glutamate receptor antagonist Glutamate 108.1

P 0878 O-Phospho-L-serine Competitive NMDA glutamate receptor antagonist with close structural similarity to L-glutamate Glutamate 108.3

H 2775 DL-threo-beta-hydroxyaspartic acid Glutamate transport inhibitor Glutamate 108.7

S 2876 Spermine tetrahydrochloride

Binds to the polyamine modulatory site of the NMDA glutamate receptor, attenuating both NMDA and quisqualate mediated responses in vivo.

Glutamate 108.7

M 5379 L-Methionine sulfoximine

Ornithine decarboxylase activator; glutamine synthetase inhibitor Glutamate 110.6

265128 5-Fluoroindole-2-carboxylic acid

Competitive inhibitor of potentiation by glycine at the NMDA glutamate receptor Glutamate 110.6

M-107 (+)-MK-801 hydrogen maleate

Highly potent and selective non-competitive NMDA glutamate receptor antagonist Glutamate 110.6

P-209Phthalamoyl-L-glutamic acid trisodium

Selective NMDA glutamate receptor agonist Glutamate 111.1

G 3126 L-Glutamine Excitatory amino acid Glutamate 111.4

M 9292 Memantine hydrochloride

Antagonist of NMDA glutamate receptors; stimulates dopamine release Glutamate 111.6

A 5282(±)-2-Amino-5-phosphonopentanoic acid


C-121 7-Chlorokynurenic acid

Potent NMDA glutamate receptor antagonist; neuroprotective. Glutamate 112.1

M 5560 (S)-MAP4 hydrochloride

Selective mGluR4,6,7 metabotropic glutamate receptor antagonist Glutamate 112.7

C 7255 Cystamine dihydrochloride Transglutaminase inhibitor; substrate analog Glutamate 113.0

A 7250 N-Acetyl-L-Cysteine Amino acid analog that partially improves neuronal survival following transient forebrain ischemia Glutamate 113.2

R 8900 Ro 8-4304 NR2B-selective, noncompetitive NMDA receptor antagonist Glutamate 114.3

A 7275 L-2-aminoadipic acid Glutamine synthetase inhibitor Glutamate 114.6

M-166 MDL 26,630 trihydrochloride

Spermidine analog that activates the polyamine site associated with the NMDA glutamate receptor Glutamate 115.9

A-167D(-)-2-Amino-7-phosphonoheptanoic acid


C 4418 L-Cysteinesulfinic Acid Putative excitatory amino acid neurotransmitter Glutamate 116.3

A 9256 L-Aspartic acid Endogenous excitatory amino acid neurotransmitter Glutamate 118.0

P 8782 (±)-cis-Piperidine-2,3-dicarboxylic acid

Excitatory amino acid; NMDA glutamate receptor agonist Glutamate 118.2

A 5157(±)-2-Amino-7-phosphonoheptanoic acid

NMDA glutamate receptor antagonist; anticonvulsant Glutamate 118.5

M 4796(±)-alpha-Methyl-4-carboxyphenylglycine

Competitive metabotropic glutamate receptor antagonist Glutamate 118.6

F 0778 Felbamate Anticonvulsant; glutamate receptor antagonist Glutamate 119.8

C 4238 CNS-1102 Noncompetitive NMDA glutamate receptor antagonist. Glutamate 120.1

A-254 AIDA Selective mGluR1 metabotropic glutamate receptor antagonist Glutamate 121.0

A-263 ATPA Selective kainate glutamate receptor agonist Glutamate 121.3

D-127 Dextrorphan D-tartrate Noncompetitive NMDA glutamate receptor antagonist. Glutamate 122.3

D-1385,7-Dichlorokynurenic acid

Potent excitatory amino acid receptor antagonist; active at the strychnine-insensitive glycine binding site of the NMDA glutamate receptor

Glutamate 122.9

P 7505 Putrescine dihydrochloride

Binds to the polyamine modulatory site of the NMDA glutamate receptor and potentiates NMDA-induced currents; precursor of spermidine

Glutamate 126.0

A 0430

1-Aminocyclopropanecarboxylic acid hydrochloride

NMDA glutamate receptor agonist acting at the glycine site Glutamate 127.7

G 2128 L-Glutamic acid hydrochloride Endogenous excitatory amino acid neurotransmitter Glutamate 128.6

C 9611 CPCCOEt Selective non-competitive mGlu1 glutamate receptor antagonist Glutamate 131.2

R-116 Riluzole Glutamate release inhibitor; anticonvulsant Glutamate 131.5

D14204 1,10-Diaminodecane

Inverse agonist at the polyamine recognition site of the NMDA glutamate receptors Glutamate 132.3

S 4250 D-Serine

Glycine mimic active at the strychnine-insensitive glycine binding site associated with the NMDA glutamate receptor as well as the inhibitory post-synaptic glycine receptor

Glutamate 134.8

C 8011 Chelidamic acid L-glutamic decarboxylase inhibitor Glutamate 136.8

A 0384 Arcaine sulfate Potent competitive antagonist of the polyamine site on the NMDA glutmate receptor Glutamate 141.8

R 7150 Ro 25-6981 hydrochloride NR2B-selective, NMDA glutamate receptor antagonist Glutamate 151.6

A-243 cis-Azetidine-2,4-dicarboxylic acid NMDA glutamate receptor modulator Glutamate 152.6

T 0625 Taurine Non-selective endogenous agonist at glycine receptors Glycine 87.7

P-204Phenylbenzene-omega-phosphono-alpha-amino acid

Selective strychnine-sensitive glycine receptor antagonist Glycine 147.5

C 8903 Clemastine fumarate H1 Histamine receptor antagonist Histamine 77.4

T 9652 Terfenadine Non-sedating H1 histamine receptor antagonist Histamine 86.1

F 9427 Fexofenadine hydrochloride H1 Histamine receptor antagonist Histamine 87.9

P 6902 Pheniramine maleate H1 histamine receptor antagonist. Histamine 88.6

D 3775 Doxylamine succinate H1 Histamine receptor antagonist Histamine 90.0

P 4651 Promethazine hydrochloride H1 Histamine receptor antagonist; anticholinergic Histamine 90.8

B 5275(+)-Brompheniramine maleate

H1 Histamine receptor antagonist Histamine 92.7

D 3630 Diphenhydramine hydrochloride H1 Histamine receptor antagonist Histamine 98.3

H 8125 L-Histidine hydrochloride Histamine precursor Histamine 98.4

C 4522 Cimetidine H2 Histamine receptor antagonist; anti-ulcer agent Histamine 98.6F 6889 Famotidine H2 Histamine receptor antagonist Histamine 99.0K 2628 Ketotifen fumarate H1 Histamine receptor antagonist Histamine 99.8

C 5040 Clemizole hydrochloride H1 Histamine receptor antagonist Histamine 100.6

M 9125 Methapyrilene hydrochloride H1 Histamine receptor antagonist Histamine 100.8

M 4910 1-Methylhistamine dihydrochloride

Histamine metabolite that crosses the blood-brain barrier Histamine 101.4

H 18774-Imidazolemethanol hydrochloride

Histonol dehydrogenase Inhibitor Histamine 101.8

C 3025(±)-Chlorpheniramine maleate


H 7250 Histamine dihydrochloride Endogenous neurotransmitter Histamine 103.1

S 5317 SKF 95282 dimaleate H2 Histamine receptor antagonist. Histamine 103.2

P 5514 Pyrilamine maleate H1 Histamine receptor antagonist Histamine 104.0L 9664 Loratadine H1 Histamine receptor antagonist Histamine 105.3

U 7500 4-Imidazoleacrylic acid Histidine ammonia-lyase and decarboxylase inhibitor Histamine 107.0

I-160

3-(1H-Imidazol-4-yl)propyl di(p-fluorophenyl)methyl ether hydrochloride


C 4915(+)-Chlorpheniramine maleate

H1 Histamine receptor antagonist; active isomer Histamine 107.1

T-123 Thioperamide maleate

Potent and selective H3 histamine receptor antagonist that crosses the blood brain barrier Histamine 107.4

I-135 Imetit dihydrobromide Potent and selective H3 histamine receptor agonist Histamine 108.3

T 6764 Triprolidine hydrochloride Potent H1 histamine receptor antagonist Histamine 111.9

B 2390(±)-Brompheniramine maleate


S-145 SKF 91488 dihydrochloride Histamine N-methyltransferase inhibitor Histamine 116.5

H-128Histamine, R(-)-alpha-methyl-, dihydrochloride

Potent, selective H3 histamine receptor agonist which crosses the blood-brain barrier; inhibits histamine synthesis and release

Histamine 127.8

R-101 Ranitidine hydrochloride H2 Histamine receptor antagonist; anti-ulcer agent Histamine 149.3

M 6383 2-methoxyestradiol Inhibitor of angiogenesis and endothelial cell proliferation Hormone 52.0

R 0500 Cortexolone Precursor of cortisol biosynthesis Hormone 63.4

R 1402 Raloxifene hydrochloride Estrogen receptor modulator; anti-estrogenic drug Hormone 79.3

D 8399 Danazol Anterior pituitary suppressant; weak androgen Hormone 84.5N 8534 Nilutamide Antiandrogen Hormone 94.2B 0385 Beclomethasone Anti-inflammatory glucocorticoid Hormone 95.1H 4001 Hydrocortisone Primary glucocorticoid secreted by the adrenal cortex Hormone 95.1F 9397 Flutamide Non-steroidal anti-androgen Hormone 98.9

A 9630 4-Androstene-3,17-dione

Testosterone precursor and metabolite with androgenic activity Hormone 99.4

D 8690(R,R)-cis-Diethyl tetrahydro-2,8-chrysenediol

Potent estrogen receptor beta antagonist; potent partial agonist at estrogen receptor alpha Hormone 99.6

P 0130 Progesterone Suppresses ovulation; induces maturation and secretory activity of the uterine endothelium Hormone 99.8

C 2505 CorticosteroneGlucocorticoid secreted by the adrenal cortex; activates both mineralcorticoid and glucocorticoid receptors

Hormone 102.0

A 5791 4-Androsten-4-ol-3,17-dione Aromatase inhibitor Hormone 102.8

A 7755 5alpha-Androstane-3alpha,17beta-diol

Testosterone metabolite; affects sperm maturation and survival Hormone 103.2

A 9755 Androsterone Anabolic steroid Hormone 103.9E 9750 Estrone Luteolytic estrogen produced by the corpus luteum Hormone 104.7

H 575217alpha-hydroxyprogesterone

Metabolite of progesterone Hormone 105.4

T 6376 Triamcinolone Synthetic glucocorticoid agonist; inducer of gene expression and apoptosis Hormone 106.2

C 3130 Cortisone 21-acetate Anti-inflammatory cortisol Hormone 107.1

D 4000trans-Dehydroandrosterone

Negative modulator of GABA-A receptors; steroid secreted by the adrenal gland with both estrogenic and androgenic properties

Hormone 107.6

C 3412 Cyproterone acetate Androgen antagonist; synthetic steroid Hormone 108.0

B 7777 Budesonide Anti-inflammatory glucocorticoid Hormone 108.7M 8046 Mifepristone Progesterone receptor antagonist Hormone 108.9

T 2408 Tolazamide Oral hypoglycemic agent; stimulates pancreatic islet cells to secrete insulin Hormone 109.8

A-178 Acetohexamide Stimulates insulin release Hormone 110.3C 1290 Chlorpropamide Stimulates insulin release Hormone 110.6E 8875 beta-Estradiol Major estrogen sectreted by premenopausal ovary Hormone 111.2

H 2270Hydrocortisone 21-hemisuccinate sodium

Hydrocortisone analog Hormone 112.5

C 30101-(2-Chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane

Antiadrenal agent; reduces corticosteroid synthesis by adrenal cortex Hormone 113.2

C 2755 Cortisone Anti-inflammatory; corticosterone analog Hormone 113.4

H 60361,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole

Specific estrogen receptor alpha (ERalpha) agonist Hormone 115.5

S 3378 Spironolactone Competitive antagonist of the cytoplasmic aldosterone receptor; diuretic Hormone 118.4

B 7005 Betamethasone SAID (steroidal anti-inflammatory drug); glucocorticoid Hormone 121.7

T 0891 Tolbutamide Oral hypoglycemic agent; stimulates pancreatic islet cells to secrete insulin Hormone 122.9

I 6138 Idazoxan hydrochloride

I2-imidazoline agonist; I1-imidazoline antagonist; alpha2-Adrenergic antagonist Imidazoline 67.9

A 9899 Antozoline hydrochloride

Imidazoline agonist; more potent than efaroxan in inducing insulin release from beta cells; H1 histamine receptor antagonist

Imidazoline 86.7

B 8433 BU99006 Irreversible I2 imidazoline binding site ligand. Imidazoline 95.9M 5685 Metrazoline oxalate Potent and selective imidazoline binding site ligand Imidazoline 100.5B 4555 Benazoline oxalate I2 Imidazoline receptor agonist Imidazoline 104.7

R-134 Rilmenidine hemifumarate Selective I1 imidazoline receptor agonist. Imidazoline 109.1

A 7127 Agmatine sulfate Endogenous agonist at imidazoline receptors; may act as a neurotransmitter Imidazoline 117.8

H 7258 Harmane I1 imidazoline binding site agonist Imidazoline 117.8

A-252 AGN 192403 hydrochloride I1 Imidazoline receptor ligand Imidazoline 133.9

B-154 BU224 hydrochloride I2 Imidazoline receptor antagonist Imidazoline 138.3

E 3263 Efaroxan hydrochloride I1 Imidazoline binding site antagonist Imidazoline 107.3

L 5025 Leflunomide

Immunosuppressive; its metabolite, a malononitrile derivative, inhibits dihydroorotate dehydrogenase (in the de novo pyrimidine synthesis pathway) and several protein tyrosine kinases

Immune System 77.3

A 2169 3 -Azido-3 -deoxythymidine

Reverse transcriptase inhibitor; active against HIV-1 virus

Immune System 79.4

P 2116 Pirfenidone Inhibitor of collagen production and fibroblast proliferation

Immune System 90.1

A 7824 6-Aminohexanoic acid

Promotes rapid dissociation of plasmin, thereby inhibiting the activation of plasminogen and subsequent fibrinolysis; inhibits plasminogen binding to activated platelets

Immune System 102.4

O 9387 OxatomideSuppresses PAF-induced bronchoconstriction; inhibits the release and actions of leukotrienes and other mediators

Immune System 104.8

A 4687 Amiprilose hydrochloride

Immunomodulator; therapeutic agent in inflammatory arthritis

Immune System 105.6

D 8296 3-deazaadenosine Antiviral Immune System 106.3

D 1413 2 ,3 -didehydro-3 -deoxythymidine Nucleoside analog; inhibits HIV replication in vitro Immune

System 106.9

B 9647 (E)-5-(2-Bromovinyl)-2 -deoxyuridine Potent inhibitor of herpes simplex type 1 Immune

System 111.0

A 4669 Acyclovir Antiviral agent Immune System 131.3

D 5782 2 ,3 -dideoxycytidine Nucleoside analog; reverse transcriptase inhibitor; antiviral

Immune System 133.5

C 3930 Calmidazolium chloride

Potent inhibitor of calmodulin activation of phosphodiesterase; strongly

Intracellular Calcium 3.5

C 7522 Calcimycin Ca2+ ionophore used to potentiate responses to NMDA, but not quisqualate glutamate receptors


T 9033 Thapsigargin Potent, cell-permeable, IP3-independent intracellular calcium releaser


A 0666

N-(4-Aminobutyl)-5-chloro-2-naphthalenesulfonamide hydrochloride

Calmodulin antagonist Intracellular Calcium 95.0

A 3281 W-7 hydrochlorideCalmodulin antagonist; inhibits Ca2+/calmodulin regulated activation of phosphodiesterase and myosin light chain kinase


T 5515 Thio-NADP sodium Blocks nicotinate adenine dinucleotide phosphate (NAADP)-induced Ca2+ release


D 9175 Dantrolene sodium Inhibits intracellular Ca2+ release from the sarcoplasmic reticulum; muscle relaxant.


861804 TMB-8 hydrochloride

Intracellular Ca2+ antagonist; inhibits calmodulin-sensitive Ca2+-ATPase activity; protein kinase C inhibitor


S 4443 SCH-28080 Potent inhibitor of gastric H+ and K+-ATPase. Ion Channels 116.6

S 5890 Sanguinarine chloride

Inhibitor of Mg2+ and Na+/K+-ATPase; isolated from the leaves and stems of Macleaya cordata and microcarpa

Ion Pump 3.2

D 0670 Dihydroouabain Sodium-potassium pump inhibitor Ion Pump 38.0

O 3125 Ouabain Blocks movement of the H5 and H6 transmembrane domains of Na+-K+ ATPases Ion Pump 46.1

A 3085 5-(N-Ethyl-N-isopropyl)amiloride Selective blocker of Na+/H+ antiport Ion Pump 69.2

A 45625-(N,N-Dimethyl)amiloride hydrochloride

Selective blocker of Na+/H+ antiport Ion Pump 80.0

R 2751 Ruthenium red Inhibits mitchondrial Ca2+ uniporter; capsaicin antagonist Ion Pump 90.0

B 2417 Benzamil hydrochloride

Selective and potent blocker of Na+/H+ and Na+/Ca2+ channels Ion Pump 97.4

M-116 Metolazone Diuretic; antihypertensive Ion Pump 98.4

D 8190 3 ,4 -Dichlorobenzamil Na+/Ca2+ exchanger inhibitor Ion Pump 98.6

L 8533 Lansoprazole Gastric proton pump inhibitor Ion Pump 98.7F 4381 Furosemide Inhibits Na+, K+ and Cl- cotransport Ion Pump 98.8

D-129 R(+)-ButylindazonePotent [K+, Cl-]-cotransport inhibitor that shows no side effects on the bumetanimide-sensitive [Na+, K+, Cl-]-cotransport system

Ion Pump 108.5

B 3023 BumetanidePotent inhibitor of the Na+-K+-2Cl- cotransporter; inhibits anthracene-9-carboxylic acid, a blocker of chloride channels

Ion Pump 111.3

A 95615-(N,N-hexamethylene)amiloride

Na+/ H+ antiport inhibitor Ion Pump 114.5

A 5585 5-(N-Methyl-N-isobutyl)amiloride Potent blocker of the Na+/H+ antiport Ion Pump 128.5

F 8257 Flunarizine dihydrochloride Ca2+/Na+ channel blocker; vasodilator Ion Pump 132.3

D 6035 Disopyramide phosphate

K+ channel modulator; anti-arrhythmic; cardiac depressant K+ Channel 20.9

D 3768 Dequalinium dichloride Selective blocker of apamin-sensitive K+ channels K+ Channel 39.1

R 3277 Rutaecarpine Delayed rectifier K+ channel blocker; inhibits platelet aggregation; vasoldilator K+ Channel 81.4

I 2279 IMID-4F hydrochloride Imidazoline-based K(ATP) channel blocker K+ Channel 81.9

P 4670 Propafenone hydrochloride

Blocks hKv1.5 and ATP-sensitive K+ channels; beta-adrenoceptor antagonist K+ Channel 86.2

B 0753 2,3-Butanedione monoxime Blocks ATP-sensitive K+ channels K+ Channel 87.4

Q 1250 Quinine sulfate

K+ channel blocker; antimalarial, anticholinergic, antihypertensive and hypoglycemic agent; alkaloid isolated from the bark of the Cinchona family of South American trees

K+ Channel 99.0

N-170 NS-1619 Selective large conductance Ca2+-activated K+-channel activator K+ Channel 99.2

P 0248 PNU-37887A Selective Kir 6.1/SUR2B potassium channel inhibitor. K+ Channel 101.8C 6019 Clotrimazole Specific inhibitor of Ca2+-activated K+ channels K+ Channel 104.2

A 0152 4-Aminopyridine Induces depolarization of GABA neurons; weak non-selective K+ Channel 105.3

G-117 Glipizide ATP-dependent K+ channel blocker K+ Channel 105.5P-154 Pinacidil K+ channel activator; antihypertensive K+ Channel 106.4

H-135 5-hydroxydecanoic acid sodium

Blocks post ischemic actions of the K+ channel activator cromakalim K+ Channel 109.9

M 4145 Minoxidil K+ channel activator; antihypertensive K+ Channel 110.9

G 0639 GlibenclamideAntidiabetic agent which blocks pancreatic ATP-dependent K+ channels resulting in an increase in intracellular Ca2+ and consequent insulin secretion

K+ Channel 112.4

D 9190 DCEBIO

Increases epithelial chloride secretion through the synergistic activation of a basolateral membrane-located K+ channel (hlK1) and an apical membrane Cl- conductance

K+ Channel 113.0

P 9872 Psora-4 Potent Kv1.3 potassium channel inhibitor. K+ Channel 118.0

D 9035 DiazoxideActivator of ATP-dependent K+ channels in both vascular smooth muscle and pancreatic beta-cells; antihypertensive

K+ Channel 126.3

H 9003 Hydroquinone Arachidonate 12-Lipoxygenase inhibitor Leukotriene 73.6

N 5023

Nordihydroguaiaretic acid from Larrea divaricata (creosote bush)

Lipoxygenase inhibitor Leukotriene 81.0

E 3520 Ebselen Antioxidant; inhibits mammalian lipoxygenases and glutathione S-transferase Leukotriene 84.7

U 1508 U-75302 BLT1 leukotriene receptor agonist Leukotriene 93.6

S 7690 SR 2640 Subtype specific CysLT1 leukotriene receptor antagonist. Leukotriene 98.0

A 3711 AA-861 5-lipoxygenase inhibitor Leukotriene 99.8

M 2692 MK-886 Potent and specific inhibitor of leukotriene biosynthesis Leukotriene 114.3

T 0318 TranilastInhibits LTC4 and PGE2 formation but does not inhibit cyclooxygenase or lipoxygenase activity; anti-asthma drug

Leukotriene 115.1

R 5523 REV 5901 Leukotriene D4 receptor antagonist Leukotriene 119.9B 4558 BWB70C Selective inhibitor of 5-lipoxygenase Leukotriene 132.3

U 6756 U-73122 Phospholipase C and A2 inhibitor that inhibits the hydrolysis Lipid 73.1

S 9318 Sandoz 58-035 Acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor Lipid 87.2

C 6643 ClofibrateAntihyperlipoproteinemic; increases lipoprotein lipase activity, thus enhancing the rate of intravascular catabolism of ULDL to IDL and LDL

Lipid 99.6

B 1552 Bromoenol lactoneCalcium-independent phospholipase A2 inhibitor; magnesium-dependent phosphatidate phosphohydrolase inhibitor

Lipid 104.0

M 3315 MJ33 Competitive and reversible inhibitor of phospholipase A2 (PLA2) Lipid 106.3

D 80087,7-Dimethyl-(5Z,8Z)-eicosadienoic acid

Phospholipase A2 and lipoxygenase inhibitor Lipid 111.6

T 8543 D-609 potassiumXanthogenate derivative with in vitro anti-tumor and anti-HIV-1 activity; inhibits phospholipase D and phosphatidylcholine phospholipase C (PIPLC)

Lipid 112.7

C 0256 Citicoline sodium Phospholipase A2 inhibitor; neuroprotective in situations of hypoxia and ischemia Lipid 114.1

R 6152 Ranolazine dihydrochloride pFOX (partial fatty acid oxidation) inhibitor Lipid 115.3

E 1779 ET-18-OCH3 Phosphoinositide-specific Phospholipase C (PI-PLC) inhibitor Lipid 138.9

L 2167 L-165,041 Peroxisome proliferator-activated receptor (PPAR) gamma agonist.

Lipid Signaling 109.1

G 5168 (Z)-Gugglesterone Bile acid receptor (FRX) antagonist. Has cholesterol lowering activity.

Lipid Signaling 123.8

M 5250 Melatonin Endogenous neurohormone which controls photo-periodic biological rhythms Melatonin 85.8

I 1899 2-Iodomelatonin Melatonin derivative with agonist activity Melatonin 90.1C 0331 6-Chloromelatonin Melatonin receptor agonist Melatonin 97.2I 5531 IIK7 Melatonin receptor agonist Melatonin 98.8A 7342 N-Acetyltryptamine Mixed agonist-antagonist at melatonin receptors Melatonin 107.6

A 1824 N-Acetyl-5-hydroxytryptamine Immediate precursor of melatonin Melatonin 107.9

K 1888 K 185 Melatonin receptor antagonist Melatonin 110.3

H 0627 6-Hydroxymelatonin Melatonin metabolite with agonist activity Melatonin 124.7

C 1610

1-(4-Chlorobenzyl)-5-methoxy-2-methylindole-3-acetic acid

NSAID; putative inhibitor of multidrug resistance-associated protein 1 (MRP1)

Multi-Drug Resistance 78.1

S 0758 Sulfaphenazole Antibacterial; inhibitor of cytochrome P4502C enzymes


F 2927

1-(4-Fluorobenzyl)-5-methoxy-2-methylindole-3-acetic acid

Putative inhibitor of multidrug resistance-associated protein 1 (MRP1)


A 3134 3-Aminopropionitrile fumarate Transformed to cyanide by cytochrome P450 in liver Multi-Drug

Resistance 95.9

P 1061 SKF-525A hydrochloride Inhibitor of microsomal drug metabolism Multi-Drug

Resistance 96.1

T 9034 Sodium Taurocholate Multi-drug resistance conjugate pathway modulator. Multi-Drug

Resistance 103.2

B 2515 L-Buthionine-sulfoximine Glutathione synthesis inhibitor Multi-Drug

Resistance 109.9

K 1003 Ketoconazole Potent inhibitor of cytochrome P450c17 enzyme; antifungal agent


B 1183

1-benzoyl-5-methoxy-2-methylindole-3-acetic acid

Putative inhibitor of multidrug resistance-associated protein 1 (MRP1)


A 1782S-(p-Azidophenacyl)glutathione

Glyoxalase and glutathione S-transferase inhibitor Multi-Drug Resistance 113.7

B 2640 DL-Buthionine-[S,R]-sulfoximine Glutathione synthesis inhibitor Multi-Drug

Resistance 116.2

A 3940 1-Aminobenzotriazole Cytochrome P450 and chloroperoxidase inhibitor Multi-Drug

Resistance 126.9

L 5647 Lidocaine hydrochloride Anti-arrhythmic; local anesthetic Na+ Channel 85.9

A 5909N-Acetylprocainamide hydrochloride

Blocks Na+ channels and appears to have Class III anti-arrhythmic activity; Na+ Channel 86.0

L 5783Lidocaine N-ethyl bromide quaternary salt

Quaternary lidocaine derivative which blocks both fast, Na+-dependent action potentials and voltage-dependent, non-inactivating Na+ conductance

Na+ Channel 93.5

M 2727 Mexiletene hydrochloride Sodium channel blocker Na+ Channel 94.8

L 1788 Lidocaine N-methyl hydrochloride Voltage-gated sodium channel blocker Na+ Channel 95.8

F 6777 Flecainide acetate Sodium channel blocker; Class I antiarrythmic agent Na+ Channel 95.9

B 2377 N-Bromoacetamide Removes fast inactivation of Na+ currents and transient K+ currents; chemical modifier Na+ Channel 96.9

Q 0875 Quinidine sulfateNa+ channel blocker and Class I antiarrythmic; alkaloid isolated from the bark of the Cinchona family of South American trees

Na+ Channel 97.3

T 4143 Triamterene Na+ channel blocker; diuretic Na+ Channel 97.9

P 9391 Procainamide hydrochloride Na+ channel blocker and Class I anti-arrhythmic Na+ Channel 101.2

T 7508 Tetracaine hydrochloride Local anesthetic Na+ Channel 101.6

P 9879 Procaine hydrochloride Na+ channel blocker Na+ Channel 106.0

P 9547 Prilocaine hydrochloride Na+ channel blocker Na+ Channel 110.3

M 0814 R(-)-Me5 Potent sodium channel antagonist Na+ Channel 112.7

P-203 Phenamil methanesulfonate

Irreversible inhibitor of amiloride-sensitive Na+ channels; derivative of amiloride Na+ Channel 113.8

D 7644 Disopyramide Sodium channel blocker; class IA antiarrhythmic Na+ Channel 114.3

A 7410 Amiloride hydrochloride Epithelial Na+ channel blocker Na+ Channel 128.3

Q 3251 Quinacrine dihydrochloride Monoamine oxidase (MAO) inhibitor; antimalarial Neurotransmi

ssion 5.0

O 2139 N-Oleoyldopamine Endogenous vanilloid; weak CB1 cannabinoid receptor ligand.

Neurotransmission 30.4

A-162

1-Amino-1-cyclohexanecarboxylic acid hydrochloride

Synthetic amino acid that crosses the blood-brain barrier


P 6777 Phenelzine sulfate Non-selective MAO-A/B inhibitor Neurotransmission 86.3

M 3778 Clorgyline hydrochloride Selective MAO-A inhibitor Neurotransmi

ssion 87.5

L 1415 L-162,313 Non-peptide AT1 angiotensin II receptor agonist Neurotransmission 88.4

C 8759 Carisoprodol Skeletal muscle relaxant Neurotransmission 90.1

N 3911 NBI 27914 CRF1 corticotropin-releasing factor receptor antagonist.


I 8250 3-Iodo-L-tyrosine Tyrosine hydroxylase inhibitor Neurotransmission 93.8

D 6940R-(-)-Desmethyldeprenyl hydrochloride

MAO-B inhibitor; metabolite of L-deprenyl Neurotransmission 96.9

120693 DL-alpha-Methyl-p-tyrosine

Inhibitor of catecholamine synthesis and tyrosine hydroxylase


I 7627 Iproniazid phosphate Monoamine oxidase inhibitor Neurotransmi

ssion 98.5

P 8511 Tranylcypromine hydrochloride MAO inhibitor; antidepressant Neurotransmi

ssion 101.1

T 6031 DL-Thiorphan Enkephalinase inhibitor Neurotransmission 102.5

2915526-Methoxy-1,2,3,4-tetrahydro-9H-pyrido[3,4b] indole

MAO inhibitor Neurotransmission 103.1

C 3635

DL-p-Chlorophenylalanine methyl ester hydrochloride

Tryptophan hydroxylase inhibitor Neurotransmission 103.6

N 1392 Nialamide Monoamine oxidase inhibitor Neurotransmission 104.0

U-106 (-)-cis-(1S,2R)-U-50488 tartrate Potent sigma receptor ligand. Neurotransmi

ssion 104.3

I 9532 Icilin Potent agonist at the CMR1 cold- and menthol-sensitive receptor.


R-106 Ro 16-6491 hydrochloride

Selective, reversible, orally-active MAO-B inhibitor which is devoid of indirect sympathomimetic activity


M 7277(±)-3-(3,4-dihydroxyphenyl)-2-methyl-DL-alanine

L-aromatic amino acid decarboxylase inhibitor; antihypertensive


C-192 Chlormezanone Anxiolytic; muscle relaxant Neurotransmission 107.1

D-131 3,5-Dinitrocatechol Selective inhibitor of catechol O-methyl Neurotransmission 107.2

P 6500 Pentylenetetrazole Non-specific CNS stimulant; convulsant Neurotransmission 107.3

M-003 R-(-)-Deprenyl hydrochloride Selective MAO-B inhibitor Neurotransmi

ssion 107.7

D-103

(±)-2,3-Dichloro-alpha-methylbenzylamine hydrochloride

Inhibitor of phenylethanolamine N-methyltransferase (PNMT); alpha2 adrenoceptor blocker


S 6633 N-Succinyl-L-proline Potent and specific angiotensin converting enzyme (ACE) inhibitor


S 8817 SB 218795 Non-peptide NK3 tachykinin receptor antagonist. Neurotransmission 110.3

M 3281alpha-Methyl-DL-tyrosine methyl ester hydrochloride

Tyrosine hydroxylase inhibitor Neurotransmission 110.6

R-107 Ro 41-1049 hydrochloride Selective, reversible, orally-active MAO-A inhibitor Neurotransmi

ssion 110.7

L 2540 L-368,899 Non-peptide oxytocin receptor antagonist. Neurotransmission 110.9

T 4425

(6R)-5,6,7,8-Tetrahydro-L-biopterin hydrochloride

Cofactor for tyrosine hydroxylase, tryptophan hydroxylase and nitric oxide synthase


H 9876 Hydroxylamine hydrochloride Monoamine oxidase inhibitor Neurotransmi

ssion 111.6

H 1753 Hydralazine hydrochloride Non-selective MAO-A/B inhibitor; antihypertensive Neurotransmi

ssion 111.9

C 4042 Captopril Angiotensin-converting enzyme (ACE) inhibitor; antihypertensive


S 2201 Semicarbazide hydrochloride Monoamine oxidase (MAO) inhibitor Neurotransmi

ssion 113.7

L 4408 Lithium Chloride Anti-manic drug used in the treatment of bipolar depression; inhibitor of inositol monophosphatase


F 4646 p-Fluoro-L-phenylalanine Substrate for tyrosine hydroxylase; arrests cells at G2 Neurotransmi

ssion 115.5

P 8013 Pargyline hydrochloride MAO inhibitor, relatively selective for MAO-B Neurotransmi

ssion 117.4

R-108 Ro 41-0960 Specific, reversible, orally-active COMT-inhibitor Neurotransmission 118.5

M 8131 L-alpha-Methyl-p-tyrosine Tyrosine hydroxylase inhibitor Neurotransmi

ssion 121.1

I-120 Iofetamine hydrochloride

Reference standard; radio-iodinated iofetamine is used to image brain blood flow


B 5559 BRL 52537 hydrochloride Kappa/mu opioid receptor agonist. Neurotransmi

ssion 125.6

D 1306 Debrisoquin sulfateAntihypertensive; metabolized to tetrahydroisoquinoline (TIQ) which may play a role in the induction of Parkinson s Disease


C-1082-Cyclooctyl-2-hydroxyethylamine hydrochloride

Inhibitor of phenylethanolamine N-methyltransferase (PNMT)


C 6506 (±)-p-Chlorophenylalanine

Depletes brain serotonin by irreversible inhibition of tryptophan hydroxylase.


D 2926 Diphenyleneiodonium chloride Endothelial nitric oxide synthase inhibitor Nitric Oxide 23.4

P 8765Ammonium pyrrolidinedithiocarbamate

Prevents induction of nitric oxide synthase (NOS) by inhibiting translation of NOS mRNA Nitric Oxide 46.7

P 1726 4-Phenyl-3-furoxancarbonitrile

Nitric oxide donor; activator of rat lung soluble guanylyl cyclase Nitric Oxide 59.5

T-173 Thiocitrulline Potent and selective inhibitor of neuronal and endothelial isoforms of nitric oxide synthase Nitric Oxide 80.3

N 5501 NG-Nitro-L-arginine Potent nitric oxide synthase inhibitor Nitric Oxide 83.6

N 4148 S-Nitrosoglutathione Nitric oxide donor in vivo Nitric Oxide 87.4

I 8768L-N5-(1-Iminoethyl)ornithine hydrochloride

Potent irreversible nitric oxide synthase inhibitor Nitric Oxide 92.0

C 9758 L-Canavanine sulfate

Selective inhibitor of inducible nitric oxide synthase (iNOS) Nitric Oxide 94.7

W 4262 1400W dihydrochloride

Selective inhibitor of inducible nitric oxide synthase (iNOS) Nitric Oxide 95.3

C 4397 Chlorzoxazone Inducible nitric oxide synthetase inhibitor; skeletal muscle relaxant Nitric Oxide 97.5

A 5006 L-Arginine Nitric oxide precursor Nitric Oxide 99.6

G 7788alpha-Guanidinoglutaric acid

Endogenous convulsant; nitric oxide synthase (NOS) inhibitor Nitric Oxide 101.2

N 5751NG-Nitro-L-arginine methyl ester hydrochloride

Competitive inhibitor of nitric oxide synthase Nitric Oxide 102.3

P 8352 1,4-PBIT dihydrobromide

Potent inducible nitric oxide synthase (iNOS) inhibitor; endothelial NOS (eNOS) inhibitor Nitric Oxide 102.6

T 73131-[2-(Trifluoromethyl)phenyl]imidazole

Potent nitric oxide synthase (NOS) inhibitor Nitric Oxide 102.8

A 8835 Aminoguanidine hydrochloride Inhibits inducible and constitutive NOS Nitric Oxide 104.0

N 7778 7-Nitroindazole Selective inhibitor of brain nitric oxide synthase Nitric Oxide 104.2

A 9834 (±)-AMT hydrochloride

Potent, selective and reversible inducible nitric oxide synthase inhibitor Nitric Oxide 104.4

D 4268N^G,N^G-Dimethylarginine hydrochloride

Reversible inhibitor of nitric oxide synthetase in vivo and in vitro Nitric Oxide 104.6

P 8227 1,3-PBIT dihydrobromide

Potent inducible nitric oxide synthase (iNOS) inhibitor; endothelial NOS (eNOS) inhibitor Nitric Oxide 105.0

I 8021L-N6-(1-Iminoethyl)lysine hydrochloride

Selective inducible nitric oxide synthase (iNOS) inhibitor. Nitric Oxide 105.8

S-154 Sepiapterin Cofactor of nitric oxide synthase; intracellularly converted to tetrahydrobiopterin . Nitric Oxide 106.2

T 7188 TFPI hydrochloride Nitric oxide synthase (NOS) inhibitor selective for neuronal isoform Nitric Oxide 106.4

B 2050 3-Bromo-7-nitroindazole Nitric oxide synthase (NOS) inhibitor Nitric Oxide 106.7

M 7033 NG-Monomethyl-L-arginine acetate

Nitric oxide synthase inhibitor; blocks formation of endothelium-derived relaxing factor (EDRF) Nitric Oxide 107.8

S 0501Sodium nitroprusside dihydrate

Releases NO in vivo, thus activating guanylyl cyclase, ADP-ribosyltransferase, and cyclooxygenase and inhibiting lipoxygenase

Nitric Oxide 109.5

N 3398 S-Nitroso-N-acetylpenicillamine Nitric oxide donor; activates soluble guanylyl cyclase Nitric Oxide 109.7

M 5171 S-Methyl-L-thiocitrulline acetate

Potent inhibitor of NOS; more potent than L-thiocitrulline Nitric Oxide 109.9

H 7278 NG-Hydroxy-L-arginine acetate

Intermediate in the conversion of arginine to NO and citrulline by NO synthase Nitric Oxide 110.9

N 7505 NADPH tetrasodium Cofactor for many enzymes, including nitric oxide synthase Nitric Oxide 112.2

A 7009 Aminoguanidine hemisulfate Selective nitric oxide synthase inhibitor Nitric Oxide 112.8

M 2901 Molsidomine Vasodilator; converted by the liver to the active metabolite, SIN-1 Nitric Oxide 114.4

E 3149 S-Ethylisothiourea hydrobromide Inhibitor of iNOS, eNOS, and nNOS Nitric Oxide 114.5

M-1843-Morpholinosydnonimine hydrochloride

Nitric oxide donor Nitric Oxide 117.7

G 4788Guanidinoethyl disulfide dihydrobromide

Selective competitive inhibitor of inducible nitric oxide synthetase (iNOS) Nitric Oxide 119.2

A 58792-(2-Aminoethyl)isothiourea dihydrobromide

Inhibits constitutive and inducible nitric oxide synthase (NOS) Nitric Oxide 125.5

M 3127 S-Methylisothiourea hemisulfate Selective inducle nitric oxide synthase inhibitor Nitric Oxide 129.5

D 5689 DM 235 Potent nootropic agent Nootropic 102.2

O 3011 Oxiracetam Nootropic agent, improves learning and memory, and prevents impairment of cognitive functions Nootropic 108.5

C 8773 Centrophenoxine hydrochloride Nootropic; cholinergic drug Nootropic 133.0

L 8539 L-687,384 hydrochloride Putative sigma-1 receptor agonist Opioid 85.6

L 4762 Loperamide hydrochloride

Meperidine congener which binds to opioid receptors; Ca2+ channel antagonist Opioid 88.5

N 7758 Naloxone hydrochloride Opioid receptor antagonist Opioid 89.5

G 3416Guanidinyl-naltrindole di-trifluoroacetate

Selective kappa opioid receptor antagonist Opioid 92.7

U-111 (-)-trans-(1S,2S)-U-50488 hydrochloride

Potent kappa opioid receptor agonist; more potent enantiomer of (±)-trans-U-50488 Opioid 94.2

N 4396 Nalbuphine hydrochloride Narcotic antagonist Opioid 94.4

L-121 Levallorphan tartrate Opioid receptor antagonist. Opioid 94.7

N-176 Naloxonazine dihydrochloride Potent mu1 opioid receptor antagonist Opioid 95.0

C-147 (+)-Cyclazocine Sigma opioid receptor antagonist Opioid 96.6

A-156(±)-N-Allylnormetazocine hydrochloride

sigma1 opioid receptor agonist; analgesic Opioid 96.8

A-114(+)-N-Allylnormetazocine hydrochloride

Selective sigma1 receptor agonist Opioid 96.9

N-165 Naloxone benzoylhydrazone

kappa3 Opioid receptor agonist; mixed mu opioid receptor agonist/antagonist Opioid 97.6

U-103 U-69593 Selective kappa opioid receptor agonist Opioid 97.7

N-156 Naltriben methanesulfonate Highly selective delta2 opioid receptor antagonist Opioid 98.3

A 3595 AC 915 oxalate Selective sigma1 opioid receptor ligand Opioid 98.5

N 1771 nor-Binaltorphimine dihydrochloride Highly selective kappa opioid receptor antagonist Opioid 98.9

U-110 (+)-trans-(1R,2R)-U-50488 hydrochloride

kappa Opioid receptor agonist; less potent enantiomer of (±)-trans-U-50488 Opioid 99.3

P 2607 PRE-084 Potent and highly selective sigma1 receptor agonist Opioid 102.4

I-122 ICI 204,448 hydrochloride

kappa Opioid receptor agonist that does not cross the blood brain barrier Opioid 103.8

D 8040 (±) trans-U-50488 methanesulfonate Selective kappa opioid receptor agonist. Opioid 105.8

N 3136 Naltrexone hydrochloride

Opioid receptor antagonist with greater potency and longer duration of action than its N-allyl congener, naloxone

Opioid 106.1

S 2812 SNC80 delta Opioid receptor agonist Opioid 107.9

N-115 Naltrindole hydrochloride

Highly selective, non-peptide delta opioid receptor antagonist that is active when administered peripherally

Opioid 112.3

C 4662 Carbetapentane citrate

Opioid receptor ligand with high affinity toward sigma1 sites; antitussive Opioid 113.5

M-120 Metaphit methanesulfonate

Competitive sigma receptor antagonist; irreversible, non-competitive antagonist at the phencyclidine site on the NMDA glutamate receptor

Opioid 113.6

U-105 U-62066 Highly selective kappa opioid receptor agonist; antitussive Opioid 113.7

N 9007 Noscapine hydrchloride Antitussive; naturally occurring opium alkaloid Opioid 117.3

M-231(-)-3-Methoxynaltrexone hydrochloride

Putative antagonist of heroin/morphine-6beta-glucuronide induced opioid activity Opioid 117.9

G-133 GR-89696 fumarate kappa Opioid receptor agonist Opioid 118.1

C-1452-Chloroadenosine triphosphate tetrasodium

P2Y receptor agonist P2 Receptor 88.5

P-178 PPADS Selective P2 receptor antagonist which blocks responses at both pre- and post-junctional sites P2 Receptor 97.3

M 7684 MRS 2159 P2X1 receptor antagonist P2 Receptor 97.4

A 4638 Azathioprine Purine analog; purine synthesis inhibitor; immunosuppressant P2 Receptor 99.8

P 2738 PPNDS tetrasodium P2X1 receptor antagonist P2 Receptor 100.0

M 3808 MRS 2179 Competitive P2Y1 receptor antagonist P2 Receptor 102.8

U 4125 Uridine 5 -diphosphate sodium P2Y receptor agonist P2 Receptor 104.7

R-115 Reactive Blue 2 P2Y receptor antagonist; most potent antagonist for ATP-activated channels P2 Receptor 106.4

M 6517

alpha,beta-Methylene adenosine 5 -triphosphate dilithium

P2 receptor agonist that is more potent than ATP at the P2X subtype P2 Receptor 107.7

N 8652 NF 023 Potent, selective P2X1 receptor antagonist P2 Receptor 107.8

A-023

2-Methylthioadenosine triphosphate tetrasodium


M-152

2-Methylthioadenosine diphosphate trisodium


A-265 ARL 67156 trisodium salt

ecto-ATPase inhibitor; prevents metabolism of P2 receptor agonists P2 Receptor 116.0

S-149 Suramin hexasodium

P2X and P2Y receptor antagonist; antiparasitic; anti-tumor agent P2 Receptor 119.1

B 0936 BRL 50481 Phosphodiesterase 7 (PDE7) inhibitor Phosphodiesterase 100.2

D 2064 Dequalinium analog, C-14 linker Protein kinase C-alpha (PKC-alpha) inhibitor Phosphorylati

on 3.2

N 1786 NSC 95397 Selective, irreversible Cdc25 dual specificity phosphatase inhibitor.

Phosphorylation 3.4

C 2932 Chelerythrine chloride

PKC inhibitor; affects translocation of PKC from cytosol to plasma membrane

Phosphorylation 3.5

Z 4626 ZM 39923 hydrochloride Janus kinase 3 (JNK-3) inhibitor. Phosphorylati

on 13.0

C 3353 CGP-74514A hydrochloride Cdk1 inhibitor Phosphorylati

on 23.8

T-182 Tyrphostin A9 Selective PDGF tyrosine kinase receptor inhibitor Phosphorylation 27.9

R 5648 Rottlerin PKC and CaM kinase III inhibitor Phosphorylation 32.0

T 2067 Tyrphostin AG 879 Tyrosine kinase nerve growth factor receptor (TrkA) inhibitor; inhibits 140 trk protooncogene and HER-2

Phosphorylation 34.8

C 7632 Cantharidin Protein phosphatase 2A inhibitor Phosphorylation 40.3

C 8088 Cantharidic Acid Protein phosphatase 1 (PP1) and 2A (PP2A) inhibitor Phosphorylation 42.3

M 6760 Myricetin Casein Kinase II inhibitor Phosphorylation 50.5

T 5318 Tyrphostin AG 808 Protein tyrosine kinase inhibitor Phosphorylation 62.4

T 4818 Tyrphostin AG 555 EGFR protein tyrosine kinase inhibitor Phosphorylation 62.6

I 0658 IC 261 Casein kinase-1 (CK-1delta/epsilon) inhibitor. Phosphorylation 66.0

E 3770

rac-2-Ethoxy-3-octadecanamido-1-propylphosphocholine

Protein kinase C (PKC) inhibitor Phosphorylation 66.2

S 9692 SU 6656 Selective Src family kinase inhibitor. Phosphorylation 66.7


P 4484 Purvalanol A Cyclin dependent kinase (CDK) inhibitor Phosphorylation 74.4

K 3888 Kenpaullone Potent inhibitor of CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E, and CDK5/p25


E 7881 Emodin p56lck Tyrosine kinase inhibitor Phosphorylation 84.2

U-120 U0126Specific inhibitor of MEK1 and MEK2 (MAP kinase kinase; MAPKK); also inhibits a constitutively active, mutant form of MEK


T 7540 Tyrphostin 47 EGFR tyrosine kinase inhibitor Phosphorylation 85.6

D1920-6 2,6-Diamino-4-pyrimidinone

Inhibitor of GTP cyclohydrolase I, the rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis; blocks the induction of nitric oxide synthesis


P 0453 Piceatannol Non-receptor kinase Syk and Lck inhibitor Phosphorylation 86.6

P 4509 Palmitoyl-DL-Carnitine chloride

Long-chain acylcarnitine; modulator of PKC activation; intermediate in mitochondrial fatty acid oxidation


E 3645

rac-2-Ethoxy-3-hexadecanamido-1-propylphosphocholine



T 4568 Tyrphostin AG 528Protein tyrosine kinase inhibitor with approximately equal potency for inhibiting EGFR-kinase activity and HER1-2-kinase activity.


S 7067 SB 202190 Highly selective, potent and cell permeable p38 MAP kinase inhibitor.


I 6391

1-(5-Isoquinolinylsulfonyl)-3-methylpiperazine dihydrochloride


D 5564 Daphnetin Protein kinase (PK) inhibitor Phosphorylation 89.0

T 6318 Tyrphostin AG 34 Protein tyrosine kinase inhibitor in human colon cancer cell lines


S 6879 Sphingosine Protein kinase C inhibitor; isolated from bovine brain cerebrosides


T 4318 Tyrphostin AG 494 Protein tyrosine kinase inhibitor. Inhibits EGF-receptor kinase activity.


I 2764 ML-7 Selective myosin light chain kinase (MLCK) inhibitor Phosphorylation 90.5

D 5919 Diacylglycerol kinase inhibitor I Diacylglycerol kinase inhibitor Phosphorylati

on 90.8

I 7016

1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride

Inhibitor of cyclic nucleotide dependent protein kinase (PKA) and protein kinase C (PKC)


T 7165 Tyrphostin 23 Protein tryrosine kinase EGFR inhibitor. Phosphorylation 91.6

T 3434 Tyrphostin AG 490 Jak-2 protein tyrosine kinase (PTK) inhibitor Phosphorylation 92.8

B 1427 H-89 cAMP-dependent protein kinase (PKA) inhibitor Phosphorylation 93.0

C 3662 Cyclosporin A Calcineurin phosphatase inhibitor; immunosuppressant


H-121 H-7 dihydrochloride Potent inhibitor of protein kinase C and cAMP-dependent protein kinase


G 6649 Genistein Cytotoxic inhibitor of tyrosine kinase and topoisomerase II kinase


I 0404 Indirubin-3 -oxime Cyclin dependent kinase (CDK) inhibitor; competes with ATP for catalytic subunit binding


H-120 HA-1004 hydrochloride

Potent inhibitor of cAMP- and cGMP-dependent protein kinases; because it has low affinity for protein kinase C, HA-1004 serves as an excellent negative control of H-7 HCl


M 9656 H-8 dihydrochloride Potent inhibitor of cAMP- and cGMP-dependent protein kinase


S 3567 SB 415286 Competitive glycogen synthase kinase-3 (GSK-3) inhibitor.


P 8139 Phorbol 12-myristate 13-acetate

Activates protein kinase C in vivo and in vitro; strong NO promoter; promotes expression of iNOS in cultured hepatocytes;T lymphocyte activator



Y 0503 Y-27632 dihydrochloride

Highly potent, cell-permeable, and selective Rho-associated coiled-coil forming protein serine/threonine kinase (ROCK) inhibitor. Also competitively inhibits ROCK-II with equal potency.


H 5257 Hispidin Potent protein kinase C-beta inhibitor Phosphorylation 96.2

L 9908 LY-294,002 hydrochloride Specific phosphatidylinositol 3-kinase (PI3K) inhibitor. Phosphorylati

on 96.9

D 1542 1,4-Dideoxy-1,4-imino-D-arabinitol Allosteric glycogen phosphorylase inhibitor Phosphorylati

on 97.2

L 8789 LFM-A13 Potent and selective inhibitor of Bruton s tyrosine kinase (BTK)


M 9440 Me-3,4-dephostatin Selective inhibitor of protein tyrosine phosphatase 1B and SHPTP-1


T 1512 Tetramisole hydrochloride

Inhibits various mammalian alkaline phosphatases (i.e., liver, kidney, placenta, bone and tumor)


C 1172 ML-9 Myosin light chain kinase (MLCK) inhibitor Phosphorylation 98.9

S 5567 SP600125 Selective c-Jun N-terminal kinase (c-JNK) inhibitor. Phosphorylation 99.7

H-123 H-9 dihydrochloride Protein kinase inhibitor most effective for cAMP- and cGMP-dependent protein kinases


S 2381 DL-Stearoylcarnitine chloride Protein kinase C (PKC) inhibitor Phosphorylati

on 101.5

S 8567 SU 4312Vascular endothelial growth factor (VEGF) receptor protein tyrosine kinase 1/2 (KDR) and platelet derived growth factor (PDGF) receptor inhibitor


P-215 PD 98,059 Specific inhibitor of the activation of mitogen-activated protein kinase kinase (MAPKK)


T 9262 Tamoxifen citrate Anti-estrogen; relatively selective protein kinase C inhibitor


D 8065 Dephostatin CD45 protein tyrosine kinase inhibitor Phosphorylation 102.9

T 7822 Tyrphostin AG 538 Insulin growth factor 1 (IGF-1) receptor protein tyrosine kinase inhibitor


E 7649 Endothall Potent inhibitor of phosphatase 2A (PP2A) Phosphorylation 106.6



D 6908 DL-erythro-Dihydrosphingosine

Protein kinase C, phospholipase A2, and phospholipase D inhibitor


T 4182 Tyrphostin AG 1478 Selective inhibitor of epidermal growth factor receptor (EGFR) protein


O 0886 Olomoucine Potent and selective inhibitor of cdc2, cdk and cyclin-dependent kinases


O 1008 Oleic Acid Activates protein kinase C in hepatocytes; uncouples oxidative phosphorylation


T 7697 I-OMe-Tyrphostin AG 538

Insulin growth factor 1 (IGF-1) receptor protein tyrosine kinase inhibitor


G 0668 GW2974 Dual EGFR and ErbB-2 receptor tyrosine kinase inhibitor


F 3764 Furegrelate sodium Thromboxane synthetase inhibitor Phosphorylation 109.2

G 6416 GW5074 cRaf1 kinase inhibitor Phosphorylation 109.3

I 1392 HA-100 Inhibitor of protein kinase A (PKA), protein kinase C (PKC) and myosin light chain kinase (MLCK)



190047S(-)-p-Bromotetramisole oxalate

Potent alkaline phosphatase inhibitor Phosphorylation 109.9

A 9501Adenosine 3 ,5 -cyclic monophosphate

PKA activator; second messenger Phosphorylation 110.0

S 8442 SU 5416 Potent and selective VEGFR PTK inhibitor; inhibits VEGF-induced angiogenesis


C 2137 Ceramide Competitive diacylglycerol kinase inhibitor; stimulator of


L 9756 (-)-Tetramisole hydrochloride Inhibits multiple mammalian alkaline phosphatases Phosphorylati

on 114.1

T 9177 Tyrphostin AG 126 Blocks production of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide in macrophages


W 1628Wortmannin from Penicillium funiculosum

Potent and specific phosphatidylinositol 3-kinase (P13-K) inhibitor


N 8784 NorcantharidinDemethylated form of cantharidin with antitumor properties; potent inhibitor of the serine/threonine protein phosphatase 2A (PP2A)



S 3442 SB 216763 Potent, selective, cell permeable inhibitor of glycogen synthetase kinase-3 (GSK-3).



R 7772 Roscovitine Potent, selective inhibitor of cyclin-dependent kinases (CDKs)


D 5794 Diacylglycerol Kinase Inhibitor II Diacylglycerol kinase inhibitor Phosphorylati

on 125.1

C 8863

7-Cyclopentyl-5-(4-phenoxy)phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine

Potent and selective Ick (src family tyrosine kinase) inhibitor.


M 4531 Meclofenamic acid sodium Cyclooxygenase and 5-Lipoxygenase inhibitor Prostaglandin 82.8

L 0664 loxoprofen Non-steroidal anti-inflammatory (NSAID) drug; analgesic Prostaglandin 83.7

M 1275 (-)-Naproxen sodium COX-1 and COX-2 inhibitor Prostaglandin 85.6

K 1751 Ketoprofen COX-1 selective non-steroidal anti-inflammatory (NSAID) drug Prostaglandin 95.6

N 0630 Niflumic acid Selective prostaglandin H synthase 2 (PGHS-2) inhibitor Prostaglandin 96.5

I-106 S(+)-Ibuprofen Active enantiomer of Ibuprofen; NSAID Prostaglandin 101.0

R 5010 Resveratrol Prevents apoptosis in K562 cells by inhibiting lipoxygenase and cyclooxygenase activity Prostaglandin 101.2

I 4883 (±)-Ibuprofen Anti-inflammatory and analgesic; non-selective COX inhibitor Prostaglandin 103.6

I 7378 IndomethacinAnti-inflammatory; antipyretic and analgesic; blocks prostaglandin biosynthesis by inhibiting prostaglandin cyclooxygenase

Prostaglandin 104.1

S 1438 Sulindac sulfone Non-steroidal anti-inflammatory compound (NSAID); metabolite of sulindac Prostaglandin 104.6

E 0516 Etodolac Non-steroidal anti-inflammatory drug (NSAID) Prostaglandin 104.8D 6899 Diclofenac sodium Cyclooxygenase inhibitor; anti-inflammatory Prostaglandin 105.1P 5654 Piroxicam Cyclooxygenase (COX) inhibitor Prostaglandin 106.1K 1136 Ketorolac tris salt Non-steroidal anti-inflammatory (NSAID) drug Prostaglandin 106.2N 1016 Nimesulide Highly selective COX-2 inhibitor Prostaglandin 114.3

M 3935 Meloxicam sodiumNon-steroidal anti-inflammatory drug (NSAID) that shows 300-fold selectivity for cyclooxygenase-2 (COX-2) vs. cyclooxygenase-1 (COX-1).

Prostaglandin 114.4

S 3065 SC 19220 EP1 Prostanoid receptor antagonist Prostaglandin 114.6

M 8878 1-Methylimidazole Anti-inflammatory; prostaglandin H synthase inhibitor; antithyroid drug Prostaglandin 114.7

S 8139 Sulindac COX inhibitor; Anti-inflammatory Prostaglandin 117.9A 5376 Acetylsalicylic acid COX inhibitor; antithrombotic Prostaglandin 122.6S 2064 SC-560 Selective COX-1 inhibitor Prostaglandin 124.9O 9637 Oxaprozin Non-steroidal anti-inflammatory drug (NSAID) Prostaglandin 125.4

A 3846 AL-8810Prostaglandin F2alpha analog with selective antagonist effects at the prostaglandin F2alpha (FP) receptor

Prostaglandin 134.7

P 8386 Phenylbutazone Anti-inflammatory; substrate for prostaglandin peroxidase Prostaglandin 137.9

B 9305 BW 245C Potent, selective DP prostanoid receptor agonist. Prostanoids 115.2

L 2411 LY-367,265 Inhibits serotonin reuptake; 5-HT2A serotonin receptor antagonist Serotonin 25.2

P 0667 Parthenolide Inhibits serotonin release from platelets; inhibits production of leukotriene B4 and thromboxane B2 Serotonin 41.8

Z-101 Zimelidine dihydrochloride Serotonin reuptake inhibitor; antidepressant Serotonin 46.3

W-108 WAY-100635 maleate Highly selective 5-HT1A serotonin receptor antagonist Serotonin 61.8

F-132 Fluoxetine hydrochloride Selective serotonin reuptake inhibitor Serotonin 75.5

L-110 LY-278,584 maleate Potent 5-HT3 serotonin receptor antagonist Serotonin 77.5

S-201 SB 224289 hydrochloride Selective 5-HT1B serotonin receptor antagonist. Serotonin 84.6

G 5793 GR 127935 hydrochloride Selective 5-HT1B/1D serotonin receptor antagonist. Serotonin 85.0

H 8250 (±)-8-Hydroxy-DPAT hydrobromide Selective 5-HT1A serotonin receptor agonist Serotonin 85.8

M 1514N-omega-Methyl-5-hydroxytryptamine oxalate salt

Serotonin receptor ligand Serotonin 86.9

S 2318 SB 228357 Selective 5-HT2B/2C serotonin receptor antagonist. Serotonin 89.6

M-110alpha-Methyl-5-hydroxytryptamine maleate

5-HT2 Serotonin receptor agonist Serotonin 89.7

M 2525 Mianserin hydrochloride Serotonin receptor antagonist Serotonin 90.2

M-204 p-MPPI hydrochloride

Selective 5-HT1A serotonin receptor antagonist which crosses the blood-brain barrier Serotonin 90.7

C 7861 Citalopram hydrobromide Selective serotonin reuptake inhibitor Serotonin 91.5

U-108 S(-)-UH-301 hydrochloride

Potent and selective 5-HT1A serotonin receptor antagonist. Serotonin 91.8

R-103 Ritanserin Potent 5-HT2 serotonin receptor antagonist which passes the blood-brain barrier Serotonin 92.3

S 1068 SB-215505 Selective 5-HT2B serotonin receptor antagonist; 100-fold higher affinity at 2B versus 2C. Serotonin 92.7

V 1889 VER-3323 hemifumarate salt 5-HT2C/5-HT2B serotonin receptor agonist. Serotonin 92.8

M-226 p-MPPF dihydrochloride Selective 5-HT1A serotonin receptor antagonist Serotonin 93.2

D-153 ( R)-(-)-DOI hydrochloride Selective 5-HT2 serotonin receptor agonist Serotonin 93.6

D 2763 Dihydroergotamine methanesulfonate

Ergot alkaloid; vasoconstrictor; competitive serotonin receptor antagonist; partial agonist at alpha adrenoceptors and D2 dopamine receptors

Serotonin 93.8

H 88765-Hydroxyindolacetic acid

Serotonin metabolite Serotonin 93.8

L 2536 LY-310,762 hydrochloride

Potent, selective 5-HT 1D serotonin receptor antagonist. Serotonin 94.0

C 7291 Clomipramine hydrochloride Serotonin reuptake inhibitor; antidepressant Serotonin 94.9

M 2381 5-Methoxy DMT oxalate Serotonin receptor agonist Serotonin 95.5

F 1553 S-(+)-Fluoxetine hydrochloride Selective serotonin reuptake inhibitor Serotonin 96.8

M-137 Methysergide maleate Serotonin receptor antagonist; antimigraine Serotonin 97.2

L-107 LY-53,857 maleate Potent and selective 5-HT2 serotonin receptor antagonist Serotonin 97.4

B 9929 BRL 15572 Potent and selective 5-HT1D serotonin receptor antagonist Serotonin 98.5

M 6628 O-Methylserotonin hydrochloride

Nonselective serotonin receptor agonist that lacks affinity for the 5-HT3 receptor Serotonin 98.6

S 0693 SB 204741 5-HT2B serontonin receptor antagonist. Serotonin 98.9

H 9772 5-Hydroxy-L-tryptophan Serotonin precursor; antidepressant; anti-epileptic Serotonin 99.4

H-140 R-(+)-8-Hydroxy-DPAT hydrobromide

Full 5-HT1A serotonin receptor agonist; active enantiomer of (±)-8-hydroxy-DPAT Serotonin 99.7

D-132N,N-Dipropyl-5-carboxamidotryptamine maleate

Selective 5-HT1A serotonin receptor agonist Serotonin 100.2

H 9523 Serotonin hydrochloride Endogenous neurotransmitter Serotonin 100.3

T 6154 Trazodone hydrochloride Atypical antidepressant Serotonin 101.0

I 7379 Imipramine hydrochloride

Tricyclic antidepressant; blocks reuptake of serotonin and norepinephrine Serotonin 101.5

Q 1004 Quipazine dimaleate Serotonin receptor agonist Serotonin 102.2

M 3668 Metergoline 5-HT1/5-HT2 Serotonin receptor antagonist; analgesic; antipyretic Serotonin 103.8

M-149 Methiothepin mesylate

5-HT1 Serotonin receptor antagonist; blocks serotonin autoreceptors Serotonin 104.2

T 8160 3-Tropanyl-3,5-dichlorobenzoate Selective 5-HT3 serotonin receptor antagonist Serotonin 104.3

P-152 S(-)-Pindolol Beta adrenergic receptor antagonist; vasodilator. Non-selective 5-HT1 serotonin receptor ligand. Serotonin 104.6

B-175 BW 723C86 5-HT2B serotonin receptor agonist Serotonin 104.9

N 3529 NAN-190 hydrobromide

Potent 5-HT1A serotonin receptor antagonist that lacks TFMPP-like stimulus properties Serotonin 105.0

P-120 1-Phenylbiguanide 5-HT3 Serotonin receptor agonist Serotonin 106.4

A 6976 Amperozide hydrochloride

Atypical antipsychotic drug with high affinity for serotonin receptors and low affinity for D2 dopamine receptors

Serotonin 106.5

D-101 (±)-DOI hydrochloride

Potent and selective 5-HT2 serotonin receptor agonist that crosses the blood brain barrier Serotonin 107.2

G 8543 GR 4661 5-HT1D serotonin receptor agonist. Serotonin 107.6

B 7148 Buspirone hydrochloride

5-HT1A Serotonin receptor agonist; non-benzodiazepine anxiolytic Serotonin 108.0

S 1688 SR 57227A Potent and selective 5-HT3 serotonin receptor agonist. Serotonin 108.3

C-1441-(m-Chlorophenyl)-biguanide hydrochloride

5-HT3 serotonergic receptor agonist Serotonin 108.4

G 6043 GR 125487 sulfamate salt 5-HT4 serotonin receptor antagonist. Serotonin 109.2

U-109 R(+)-UH-301 hydrochloride

Potent and selective 5-HT1A serotonin receptor agonist Serotonin 109.8

C 55541-(3-Chlorophenyl)piperazine dihydrochloride


Q-107 Quipazine, N-methyl-, dimaleate

Tertiary amine analog of quipazine which binds to 5-HT3 serotonin receptors with an affinity similar to that of quipazine, but which lacks affinity for central 5-HT1B serotonin receptors

Serotonin 110.2

C 6022 Cyproheptadine hydrochloride 5-HT2 serotonin receptor antagonist Serotonin 110.4

S-0031-(1-Naphthyl)piperazine hydrochloride

5-HT2 serotonin receptor antagonist Serotonin 110.5

S-180 SB 206553 hydrochloride Potent 5-HT2C/5-HT2B serotonin receptor antagonist Serotonin 111.3

S 0443 SB 203186 5-HT4 serotonin receptor antagonist. Serotonin 111.6R 0875 Reserpine Inhibits vesicular catecholine and serotonin uptake. Serotonin 111.6

T-1133-Tropanylindole-3-carboxylate methiodide

Potent, water soluble 5-HT3 serotonin receptor antagonist Serotonin 111.9

Q-109 Quipazine, 6-nitro-, maleate Potent and selective serotonin reuptake inhibitor Serotonin 112.9

S-103 Spiroxatrine Partial 5-HT1A serotonin receptor agonist Serotonin 113.3

C 4542 Cyclobenzaprine hydrochloride 5-HT2 serotonin receptor antagonist Serotonin 113.3

C-106 CGS-12066A maleate 5-HT1B Serotonin receptor agonist Serotonin 113.7

246557 Tryptamine hydrochloride Serotonin receptor ligand Serotonin 114.6

S 3313 SB 204070 hydrochloride Selective 5-HT4 serotonin receptor antagonist Serotonin 114.8

P-126 Pirenperone 5-HT2 Serotonin receptor antagonist Serotonin 115.2

T 3146 Trimipramine maleate

Serotonin reuptake inhibitor that also blocks norepinephrine reuptake; antidepressant Serotonin 115.3

S-009 PAPP Selective 5-HT1A serotonin receptor agonist Serotonin 116.2

T-1043-Tropanyl-indole-3-carboxylate hydrochloride

Selective 5-HT3 serotonin receptor antagonist Serotonin 116.3

B-173 BRL 54443 maleate Potent 5-HT1E/1F serotonin receptor agonist Serotonin 118.6

S 7389 SB 269970 hydrochloride Selective 5-HT7 serotonin receptor antagonist Serotonin 119.4

F 2802 Fluvoxamine maleate Selective serotonin reuptake inhibitor Serotonin 120.0

R-140 Ro 04-6790 dihydrochloride Selective 5-HT6 serotonin receptor antagonist. Serotonin 121.0

F 1678 R-(-)-Fluoxetine hydrochloride Selective serotonin reuptake inhibitor Serotonin 121.7

T 0254 L-Tryptophan Antidepressant; precursor of serotonin Serotonin 123.8

M-1092-Methyl-5-hydroxytryptamine maleate


C-1175-Carboxamidotryptamine maleate


A-164 Alaproclate hydrochloride Potent and selective serotonin reuptake inhibitor Serotonin 130.2

S 0568 SB 200646 hydrochloride 5-HT 2C/2B serotonin receptor antagonist. Serotonin 130.5

S-0081-(2-Methoxyphenyl)piperazine hydrochloride

Selective 5-HT1 serotonin receptor agonist Serotonin 131.8

G 5918 GR 113808 5-HT4 serotonin receptor antagonist. Serotonin 132.7S-006 Ketanserin tartrate Selective 5-HT2 serotonin receptor blocker Serotonin 134.5

B-134 BMY 7378 dihydrochloride

Partial 5-HT1A serotonin receptor agonist; alpha1D adrenoceptor antagonist Serotonin 135.2

S-174 SDZ-205,557 hydrochloride

Potent and selective 5-HT4 serotonin receptor antagonist Serotonin 139.2

M 6500 Cysteamine hydrochloride

Induces duodenal ulcers in rats, potent depletion of prolactin concentrations in pituitary tissue in vivo and in vitro and depletion of somatostatin concentrations.

Somatostatin 95.6

S 1316 Seglitide Selective sst2 somatostatin receptor agonist Somatostatin 103.2

P 7340

(±)-threo-1-Phenyl-2-decanoylamino-3-morpholino-1-propanol hydrochloride

Glucosylceramide synthase inhibitor; blocks formation of glucosylceramide from ceramide Sphingolipid 77.3

O 0383 N-Oleoylethanolamine

Ceramidase inhibitor; inhibits sphingolipid signaling pathway Sphingolipid 99.6

C 1159 L-Cycloserine Blocks sphingosine biosynthesis by inhibition of ketosphinganine synthetase Sphingolipid 101.7

C 7005 DL-CycloserineAlanine aminotransferase inhibitor; blocks sphingosine biosynthesis by inhibition of ketosphinganine synthetase

Sphingolipid 115.9

L-119 L-703,606 oxalate Potent and selective non-peptide NK1 tachykinin receptor antagonist Tachykinin 81.3

W-104 WIN 62,577 NK1 tachykinin receptor antagonist Tachykinin 88.2

L-137 L-733,060 hydrochloride NK1 tachykinin receptor antagonist Tachykinin 100.7

S 5192 SB 222200 Non-peptide NK3 tachykinin receptor antagonist. Tachykinin 105.9

A 5330 L-732,138

Competitive antagonist at substance P receptors; approximately 1000-fold more potent at cloned human NK-1 receptors than at cloned human NK-2 and NK-3 receptors

Tachykinin 123.4

L 9539 L-655,240 Thromboxane A2 (TXA2) receptor antagonist Thromboxane 101.8

P 8477 Picotamide Eicosenoid receptor antagonist; a thromboxane A2 antagonist; antiplatelet agent Thromboxane 149.2

R 3255 13-cis-retinoic acid Anti-inflammatory and antitumor actions mediated through RAR-beta and RAR-alpha receptors Transcription 62.4

N 8403 6-Nitroso-1,2-benzopyrone

Poly(ADP-ribose) polymerase (PARP) ligand which preferentially destabilizes one of the two zinc-fingers inactivating the enzyme

Transcription 66.6

M 6191 GW9662 Irreversible peroxisome proliferator-activated receptor-gamma (PPAR-gamma) inhibitor Transcription 77.0

T 3757 TTNPBSelective and highly potent retinoic acid analog with affinity for retinoic acid receptors (RAR) alpha, beta, and gamma

Transcription 92.2

C 0330 CiprofibratePeroxizome proliferator;specific ligand for the nuclear peroxisome proliferator-activated receptor alpha (PPARalpha)

Transcription 96.2

P 8852 6(5H)-Phenanthridinone Poly(ADP-ribose) Polymerase (PARP) inhibitor Transcription 103.0

T 1443 TCPOBOPConstitutive androstane receptor (CAR) agonist; most potent known member of the phenobarbital-like class of CYP-inducing agents

Transcription 104.1

F 6020 Fenofibrate PPAR-alpha receptor agonist; lipid regulating drug Transcription 109.2

D 1916D-ribofuranosylbenzimidazole

Inhibitor of RNA synthesis; chain terminator Transcription 113.8

T 1698 Tetradecylthioacetic acid

Peroxisome proliferator-activated receptor (PPAR)-alpha agonist Transcription 116.5

G 5668 GW1929 High affinity peroxisome proliferator-activated gamma (PPAR-gamma) agonist Transcription 118.7

G 6793 GW7647 Potent agonist of peroxisome proliferator-activated alpha (PPAR-alpha) Transcription 143.2

M 1022 Dihydrocapsaicin Capsaicin analog Vanilloid 71.5

C-191 Capsazepine Synthetic analog of capsaicin that acts as a specific vanilloid receptor antagonist Vanilloid 97.7

V 9130 N-Vanillylnonanamide Synthetic analog of capsaicin with similar bioactivity Vanilloid 102.5

S 0441 SB-366791 Vanilloid receptor-1 (VR1) antagonist Vanilloid 103.9

E 0137 Vanillic acid diethylamide CNS and respiratory stimulant Vanilloid 106.0

NSC # Drug Name Description Class

% Survival index at screening Conc of 1 µM (average of 2 runs)

218321 Pentostatin Inhibitor of adenosine deaminase Adenosine 140.0

141540 Etoposide Topoisomerase II inhibitor; induces apoptosis; cell cycle inhibitor Apoptosis 19.7

92859 Arsenic trioxide DNA fragmentation and apoptosis inducer Apoptosis 122.8721517 Zolendronic acid Bisphosphonate, prevents bone loss by inhibiting osteoclast migration and maturationCell Biology 101.338721 Mitotane Adrenal cytotoxic agent, modifies peripheral metabolism of steroids,Suppresses adrenal cortexCell Biology/Adrenal gland function130.4712807 Capecitabine Thymidylate synthase inhibition and incorporation into RNA and DNA Cell Cycle 105.2

19893 Fluorouracil Thymidylate synthetase inhibitor; pyrimidine analog, leads to accumulation of cells in S phase Cell Cycle 107.3

296961 AmifostineRadioprotective agent; selectively protects normal tissues from the damaging effects of anti-neoplastic radiation therapy

Cell Stress 102.8

1390 Allopurinol Xanthine oxidase inhibitor; inhibits the final step in uric acid biosynthesis Cell Stress 115.9

169780 Dexrazoxone Cardioprotectant, chelating agent, interferes with iron mediated free radical generationCell Stress 131.8

49842 Vinblastine sulfate Inhibitor of microtubule assembly Cytoskeleton and ECM 36.8

67574 Vincristine sulfate Inhibitor of microtubule assembly Cytoskeleton and ECM 38.6

747973 Ixabepilone Microtubule inhibitor Cytoskeleton and ECM43.3

NCI Approved Oncology Drug Set II Screening Results

125973 Paclitaxel Microtubule hyperstabilization, blocks mitotis Cytoskeleton and ECM47.1608210 Vinorelbine tartrate Tubulin interactor, mitotis inhibitor Cytoskeleton and ECM54.7628503 Docetaxel Promotes and stabilizes Microtubule assembly Cytoskeleton and ECM62.6

702294 Estramustine disodium phosphate Microtubule inhibition


66847 Thalidomide Selective inhibitor of the biosynthesis of tumor necrosis factor a (TNF-alpha); angiogenesis inhibitor


82151 Daunorubicin HCl Topoisomerase II inhibitor, DNA intercalation DNA 1.6246131 Valrubicin DNA Topoisomerase II inhibitor DNA 2.3609699 Topotecan HCl topoisomerase I inhibitor. DNA 3.824559 Plicamycin DNA binding in presence of cations and inhibits RNA synthesisDNA 12.33053 Dactinomycin DNA binding, inhibits transcription DNA 41.3105014 Cladribine DNA interacalation and DNA damage DNA 49.6613327 Gemcitabine HCl Nuceloside analog DNA 64.4762 Nitrogen mustard Alkylating agent DNA 70.826980 Mitomycin C DNA crosslinking DNA 78.3312887 Fludarabine Nuceloside Analog DNA 92.1127716 Decitabine Cytidine/Nuceloside Analog DNA 98.4686673 Nelarabine Nuceloside Analog DNA 99.0266046 Oxaliplatin Alkylating agent DNA 101.8

63878 Cytarabine hydrochloride Synthetic nucleoside analog DNA 104.0

616348 Irinotecan HCl Topoisomerase I inhibitor DNA 104.7102816 Azacitidine Cytidine/Nuceloside Analog DNA 105.06396 Thiotepa Alkylating agent DNA 107.325154 Pipobroman Alkylating agent DNA 108.079037 Lomustine, CCNU Alkylating agent DNA 109.7755 Mercaptopurine Inhibits purine nucleotide synthesis, Immunosuppresive drugDNA 110.1752 Thioguanine DNA interacalation and DNA damage DNA 110.7

27640 Floxuridine Pyrimidine Analog DNA 111.1750 Busulfan Alkylating agent DNA 111.485998 Streptozocin Alkylating agent, DNA damage DNA 113.1

77213 Procarbazine hydrochloride Alkylating agent DNA 114.0

45923 Methoxsalen DNA crosslinking DNA 115.1362856 Temozolomide Alkylating agent DNA 117.1241240 Carboplatin Antineoplastic, Alkylating Agent DNA 117.5

26271 Cyclophosphamide Cancer chemotherapeutic; cross-links DNA, alkylating agent DNA 120.2

698037 Pemetrexed Inhibits purine and pyrimidine synthesis DNA 120.734462 Uracil mustard Alkylating agent DNA 123.614229 Acrichine DNA Intercalation, antimalarial DNA 123.7409962 Carmustine DNA alkylating agent; causes interstrand crosslinks DNA 125.645388 Dacarbazine Alkylating agent DNA 126.3

9706 Triethylenemelamine Alkylating agent DNA 126.9

3088 Chlorambucil DNA crosslinker; induces apoptosis DNA 127.0

119875 CisplatinInduces intrastrand DNA crosslinks; effects are regulated by kinases, phosphatases and Ca2+/calmodulin

DNA 127.8

109724 Ifosfamide Alkylating agent DNA 129.2123127 Doxorubicin HCl Topoisomerase II inhibitor, DNA Intercalation DNA 2.2122819 Teniposide Topoisomerase II inhibitor, DNA dsbreaks DNA Repair 7.4

279836 Mitoxantrone DNA synthesis inhibitor, Topoisomerase II inhibitor DNA Metabolism 1.3

8806 Melphalan Antineoplastic; forms DNA intrastrand crosslinks by bifunctional alkylation in 5 -GGC sequences

DNA Metabolism 94.3

32065 Hydroxyurea Antineoplastic; inactivates ribonucleoside reductase which blocks the synthesis of deoxynucleotides


740 Methotrexate Folic acid antagonist, dihydrofolate reductase (DHFR) inhibitor, DNA synthesis DNA Metabolism106.3

13875 Altretamine Antineoplastic, Alkylating Agent DNA Metabolism 110.0

606869 Clofarabine Disrupts DNA synthesis and causes fatal replication errorsDNA Repair 33.1125066 Bleomycin Induction of DNA strand breaks DNA Repair 104.3701852 Vorinostat Histone Deacetylase Inhibitor Gene Regulation and Epigenetics38.4713563 Exemestane False substrate for the aromatase enzyme involved in estrogen biosynthesisHormone 96.1719276 Fulvestrant Estrogen Receptor Antagonist Hormone 99.0719345 Letrozole Inhibits the enzyme aromatase through competitive inhibition, which is responsible for converting androgens to estrogensHormone 100.5747974 Raloxifene HCl Estrogen receptor modulator; anti-estrogenic drug Hormone 103.571423 Megestrol acetate Synthetic derivative of Progesterone Hormone 104.2719344 Anastrozole Inhibits the enzyme aromatase through competitive inhibition, which is responsible for converting androgens to estrogensHormone 105.0369100 Imiquimod Immune response modifier, through TLR-7 Immune System98.7747972 Lenalidomide Immunomodulatory, anti-apoptotic Immune system100.1

18509 Aminolevulinic acid Accumulation of fluorescent porphyrins, miscellaneous topical agent

Light sensitivity 114.7

733504 Everolimus Blocks mTOR mTOR 80.1226080 Rapamycin mTOR inhibitor mTOR 115.8745750 Lapatinib Tyrosine kinase activity, (EGFR, HER2) Phosphorylation96.7747599 Nilotinib Tyrosine kinase inhibitor Phosphorylation98.0

180973 Tamoxifen citrate Anti-estrogen; relatively selective protein kinase C inhibitor


732517 Dasatinib Bcr/Abl and Scr family tyrosine kinase inhibitor Phosphorylation104.3750690 Sunitinib Targets multiple receptor tyrosine kinases, PDGFR, VEGFRPhosphorylation105.7718781 Erlotinib HCl EGFR Inhibitor Phosphorylation106.3715055 Gefitinib EGFR Inhibitor Phosphorylation109.7743414 Imatinib Inhibits tyrosine kinase enzymes, Bcr-abl Phosphorylation110.4747971 Sorafenib Kinase inhibitor, serine/threonine and receptor tyrosine kinasesPhosphorylation119.1719627 Celecoxib Inhibition of prostaglandin synthesis Prostaglandin 113.8

681239 Bortezomib Proteasome Inhibitor Proteasome 8.4122758 Tretinoin Binds to retinoic acid receptors Transcription 95.7Reference :

Drug Name Description Class

% Survival index at screening Conc of 10 µM

Bithionol Bacteristatic antihelmintic Antihelmintic 120.7Hexachlorophene Antiseptic and Germicide Antiseptic 81.3MAL2-11B ATPase Inhibitor ATPase 92MAL3-101 ATPase Inhibitor ATPase 87DMT3084 ATPase Inhibitor ATPase 99MAL2-51 ATPase Inhibitor ATPase 93

References :

Nutlin-3 ( Sigma # N6287) Inhibits p53-MDM2 Interaction p53 12.6

YH264A Inhibits p53-MDM2 Interaction p53 92.7YH265A Inhibits p53-MDM2 Interaction p53 99.1KK_NW_16A Inhibits p53-MDM2 Interaction p53 99.6

References :

Wright CM, Seguin SP, Fewell SW, Zhang H, Ishwad C, Vats A, Lingwood CA, Wipf P, Fanning E, Pipas JM, Brodsky JL.Inhibition of Simian Virus 40 replication by targeting the molecular chaperone function and ATPase activity of T antigen.Virus Res. 2009 Apr;141(1):71-80.S. P. Seguin et al., High-Throughput Screening Identifies a Bisphenol Inhibitor of SV40 Large T Antigen ATPase Activity. Journal of biomolecular screening, (Sep 23, 2011).

Czarna, A., et al. Robust generation of lead compounds for protein-protein interactions by computational and MCR chemistry: p53/Hdm2 antagonists. Angewandte Chemie 49, 5352-5356 (2010).

Popowicz, G.M., et al. Structures of low molecular weight inhibitors bound to MDMX and MDM2 reveal new approaches for p53-MDMX/MDM2 antagonist drug discovery. Cell cycle 9, 1104-1111 (2010).

The NCI/DTP Open Chemical Repository, http://dtp.cancer.gov

Bayesian Hierarchical Changepoint Analysis of the Effect ofYM-155 and Bortezomib on Tumor Xenograft Volume

August 28, 2011

1 Model Setup

The hierarchical Bayes piecewise linear model [1] previously presented, with a change of param-eterization to enhance sharing of information, was employed, where the groups are indexed asfollows:

i Cell Line Treatment # Animals1 MKL-1 Bortezomib 212 MKL-1 Saline 313 MKL-1 YM155 234 MS-1 Saline 55 MS-1 YM155 66 UISO Saline 57 UISO YM155 5

Table 1 Experimental group label definitions and sample sizes.

This is a hierarchical Bayesian model, where animal ij has four model parameters: the nadir log-volume (aij), growth delay time (erij ), pre-nadir shrinkage rate (eb1ij ) and post-nadir growth rate(eb2ij ). The values of rij, b1ij and b2ij are exponentiated to ensure they are positive. The animal-level parameters are distributed around a corresponding treatment group-level parameter, as de-scribed in Block 2, below. The treatment group-level parameters are centered around a mean meta-parameter (Block 4, below), which allows for sharing of information between treatment groups.This is of particular value in this model, where, in some treatment groups (e.g., Saline), there is notumor shrinkage, so the growth delay is pushed towards zero, and there is then no information toestimate the rate of tumor shrinkage (because there is no shrinkage), but the sharing of informationenhances numerical stability by defaulting the vanishingly short tumor shrinkage period to have atumor shrinkage rate with a sensible, if irrelevant value.

The model accommodates volumes below the limit of quantitation, which are generally recordedas zero. We take volumes coded as zero to be values below the limit of quantization (LQ), wherethe limit of quantitation is defined to be the smallest non-zero value; for the present data set,that volume equals 4mm3 (log2(4) = 2). BLQ volumes are utilized in the estimation process,considered left-censored at LQ.

The complete model parameterization is presented in the following blocks, where N (µ, τ) is anormal distribution with mean µ and precision τ, and G(σ, η) is a gamma distribution with scale σand shape η (mean σ/η and variance σ/η2):

1

1. Piecewise linear model for log-volume

µij(t) = aijt + eb1ijmax(erij − t, 0) + eb2ijmax(t− erij , 0)ωij(t) = eθµij(t)

log2(vij)(t) ∼ N (µij(t), ωij(t))

2. Animal-Level regression parameters

aij ∼ N (αi, τa)

b1ij ∼ N (β1i, τb1)

b2ij ∼ N (β2i, τb2)

rij ∼ N (ρi, τa)

3. Experimental group regression parameters

αi ∼ N (α, τα)

β1i ∼ N (β1, τβ1)

β2i ∼ N (β2, τβ2)

ρi ∼ N (ρ, τρ)

4. Mean meta-parameters

α ∼ N (0, 0.01)

β1 ∼ N (0, 0.01)

β2 ∼ N (0, 0.01)

ρ ∼ N (0, 0.01)

θ ∼ N (0, 0.01)

5. Dispersion meta-parameters

τa ∼ G(0.1, 0.1) τα ∼ G(0.1, 0.1)τb1 ∼ G(0.1, 0.1) τβ1 ∼ G(0.1, 0.1)τb2 ∼ G(0.1, 0.1) τβ2 ∼ G(0.1, 0.1)τr ∼ G(0.1, 0.1) τρ ∼ G(0.1, 0.1)

The most interpretable parameters are in Block 3, Experimental group regression parameters. Dif-ferences in these parameters will represent differences between, for instance, growth delay ratesbetween treatments.

2

2 Parameter Estimates

Parameters as described in the Model Setup section were estimated using JAGS (Just AnotherGibbs Sampler) with 20,000 MCMC iterations. Traces of the estimated parameters were checkedvisually for convergence. The relationship of all the estimated parameters to the data can bechecked visually in the section Animal-Level Model; the numerical estimates of the treatment-level parameters are presented here with 95% credible intervals.

αi eβ1i eβ2i eρi

MKL-1 Bortezomib 5.5(5,6) 0.00069(6.1e-12,1.4) 0.32(0.28,0.35) 1.3e-05(7.7e-21,0.053)MKL-1 Saline 5.3(4.9,5.7) 0.00037(5.5e-10,0.1) 0.4(0.37,0.44) 1.1e-05(1.3e-10,0.041)

MKL-1 YM155 4.1(3.6,4.6) 0.0014(3.5e-08,0.025) 0.37(0.33,0.41) 5.5(2.6,9.5)MS-1 Saline 4.4(3.4,5.3) 0.00053(2.2e-10,0.61) 0.21(0.17,0.26) 2.2e-05(3.3e-19,0.19)

MS-1 YM155 4.4(3.5,5.2) 0.00049(2.2e-11,0.35) 0.19(0.16,0.23) 5.6e-06(5.6e-20,0.17)UISO Saline 2.4(1.5,3.5) 0.00055(3.3e-10,0.26) 0.19(0.16,0.23) 1.7e-05(5.2e-16,1.5)

UISO YM155 2.6(1.5,3.6) 0.00025(1.6e-11,0.017) 0.23(0.19,0.28) 11(3.1,36)

Table 2 Estimated values and 95% credible intervals for nadir volume (αi), shrinkage rate (eβ1i),growth rate (eβ2i) and time to nadir (eρi).

The most notable feature of the estimates is the increased delay in growth in animals with MKL-1and UISO tumors treated with YM155 (5.5 and 11 days, respectively). Animals with MS-1 tumorsso treated experienced no such apparent delay in growth. Tumors with delay in growth did notshrink prior to the resumption of growth (eβ1i ≈ 0). The post-nadir growth rates of all the animalswith MKL-1 tumors were similar, and faster than MS-1 and UISO tumors. The estimated nadir(αi) appears smaller for the UISO tumors, but the nadir value may be confounded with the baselinetumor volumes, which are significantly smaller in the UISO tumors than the others, as displayedin Figure 1.

3

●

●●

●●

●

●●●●

1 2 3 4 5 6 7

23

45

67

Experimental Group

log 2

(Day

0 V

olum

e)

Figure 1 Day 0 volumes (base 2 log-transformed). The experimentalgroups are defined in Table 1; groups 6 and 7 are UISO Saline and YM155,respectively.

4

3 Plots by Treatment and Cell Line

The panels of curves in Figures 2 and 3 represent the summary of the population model for theseven experimental groups. The red lines indicate the central estimates, while the shaded areas95% credible regions (Bayesian confidence regions) for the growth curves. The credible regionsare wider for the experimental groups with fewer animals. It is seen that there is evidence ofgrowth delay for the YM155-treated animals with MKL-1 and UISO tumors, but not for the otherexperimental groups. It is also seen that the YM155 does not uniformly suppress tumor growth; itappears to have no effect on some tumors, while delaying growth a great deal more than averagein others. Figure 2 displays the population estimates against the observed tumor volume profiles,demonstrating the correspondence between the population estimates and the raw data, while Figure3 displays the population- and animal-level models together, to demonstrate the correspondencebetween the animal-level and population-level models.

5

0 10 20 30 40 50

24

68

10

Day

log 2

(Vol

ume)

MKL−1: Bortezomib

0 10 20 30 40 50

24

68

10

Day

log 2

(Vol

ume)

MKL−1: Saline

0 10 20 30 40 50

24

68

10

Day

log 2

(Vol

ume)

MKL−1: YM155

0 10 20 30 40 502

46

810

Day

log 2

(Vol

ume)

MS−1: Saline

0 10 20 30 40 50

24

68

10

Day

log 2

(Vol

ume)

MS−1: YM155

0 10 20 30 40 50

24

68

10

Day

log 2

(Vol

ume)

UISO: Saline

0 10 20 30 40 50

24

68

10

Day

log 2

(Vol

ume)

UISO: YM155

Figure 2 Population tumor volume growth curves for the seven experi-mental groups. The bold red lines are the central estimates, while the shadedregions are 95% credible intervals. Individual animal growth curves are rep-resented by grey lines. The limit of quantitation is 2 on this scale; 0 volumesare represented as 2.

6

0 10 20 30 40 50

24

68

10

Day

log 2

(Vol

ume)

MKL−1: Bortezomib

0 10 20 30 40 50

24

68

10

Day

log 2

(Vol

ume)

MKL−1: Saline

0 10 20 30 40 50

24

68

10

Day

log 2

(Vol

ume)

MKL−1: YM155

0 10 20 30 40 502

46

810

Day

log 2

(Vol

ume)

MS−1: Saline

0 10 20 30 40 50

24

68

10

Day

log 2

(Vol

ume)

MS−1: YM155

0 10 20 30 40 50

24

68

10

Day

log 2

(Vol

ume)

UISO: Saline

0 10 20 30 40 50

24

68

10

Day

log 2

(Vol

ume)

UISO: YM155

Figure 3 Population tumor volume growth curves for the seven experi-mental groups. The bold red lines are the central estimates, while the shadedregions are 95% credible intervals. Modeled individual animal growthcurves are represented by blue lines.

7

4 Animal-Level Model Fit

The Figures 4.1-4.12 confirm the fit of the model to the data. Circles are the observed data, bluelines are the animal-level models (based on aij, b1ij, b2ij and rij, for the ith animal in the j th group),and the red lines are the experimental group-level model (based on αj, β1j, β2j and ρj, for the ith

animal in the j th group)). The animals are sorted according to the experimental group in Table 1.

8

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●●

● ● ●●

MKL−1 Bortezomib

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●●

●●

● ● ●●

● ●●

MKL−1 Bortezomib

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●

● ●●

MKL−1 Bortezomib

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●●● ●

MKL−1 Bortezomib

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●●

●●

● ●

MKL−1 Bortezomib

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

● ●●

● ●

MKL−1 Bortezomib

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●

●

● ●

●

●● ●

● ●

MKL−1 Bortezomib

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●

●

● ●●

●● ●

●

MKL−1 Bortezomib

Figure 4.1 Animal-level plots. Circles are data, blue lines animal-level model, red lines experi-mental group-level model.

9

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

● ●

●

●● ●

●

MKL−1: Bortezomib

4.80.00068

0.341.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●

●●

● ●

●

MKL−1: Bortezomib

5.50.00069

0.361.1e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

● ●

●● ●

●● ●

MKL−1: Bortezomib

6.10.00069

0.281.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●●

●● ●

●

MKL−1: Bortezomib

5.70.00069

0.331.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●●

●

●●

MKL−1: Bortezomib

5.27e−04

0.431.1e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

● ●●

●●

●● ●

MKL−1: Bortezomib

4.90.00069

0.321.2e−05

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

● ●

●

●

●●

●●

MKL−1: Bortezomib

5.10.00068

0.41.2e−05

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●●

●

● ●

●

●●

● ●●

MKL−1: Bortezomib

3.50.00066

0.361.2e−05

Figure 4.2 Animal-level plots. Open circles are data, filled circles are BLQ, blue lines animal-level model, red lines experimental group-level model. Values are (top to bottom) ai, eb1i , eb2i , eri .

10

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

● ●

●

●●

●

MKL−1: Bortezomib

70.00069

0.381.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

● ●

●● ●

● ●●

●

MKL−1: Bortezomib

5.40.00069

0.321.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●●

●●

●● ●

●

MKL−1: Bortezomib

5.70.00071

0.371.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●● ●

● ●

●●

●

MKL−1: Bortezomib

4.60.00069

0.351.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●●

●●

●

● ●● ●

●● ● ●

●

MKL−1: Bortezomib

6.10.00071

0.21.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●● ●

●

●

MKL−1: Saline

6.80.00037

0.341.2e−05

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●

●

● ●

●●

MKL−1: Saline

6.40.00039

0.391.2e−05

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●

●

●●

●

●● ●

●

MKL−1: Saline

5.20.00038

0.341.2e−05


11

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●●

●

●●

MKL−1: Saline

50.00037

0.411.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ●

●●

●

●●● ●

●

MKL−1: Saline

5.90.00037

0.291.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●●●

●●●

●

MKL−1: Saline

5.40.00037

0.321.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●●

●●

●●

MKL−1: Saline

6.90.00036

0.411.1e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

● ●●

●●

● ●●

MKL−1: Saline

5.50.00037

0.351.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

● ●

●●

● ●● ●

MKL−1: Saline

5.40.00037

0.321.2e−05

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●

● ● ●●

● ●

● ●● ●

●

MKL−1: Saline

4.60.00038

0.281.1e−05

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●

●

●

●●

●●●

MKL−1: Saline

5.40.00036

0.391.2e−05


12

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ●

●

●

●●

● ●●

● ●

MKL−1: Saline

4.74e−04

0.341.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●●

●

● ● ●

MKL−1: Saline

6.40.00039

0.391.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●●

● ●

●●

●

●

MKL−1: Saline

4.30.00037

0.451.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ● ●

● ●●

●●

● ●

MKL−1: Saline

3.30.00038

0.371.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ●

●●

●

● ●

MKL−1: Saline

6.10.00038

0.391.1e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ●●

●

● ●

●●

●●●

MKL−1: Saline

4.60.00038

0.351.2e−05

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●

●

●

●●

●

MKL−1: Saline

6.20.00039

0.421.2e−05

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●

●

●

●●

MKL−1: Saline

7.70.00038

0.51.2e−05


13

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●●

●●

●●

●

MKL−1: Saline

5.30.00037

0.351.1e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●●

●●

MKL−1: Saline

5.74e−04

0.531.1e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●

●

MKL−1: Saline

6.14e−04

0.531.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ●●

●

●●

●

MKL−1: Saline

4.40.00037

0.421.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●

●

●

MKL−1: Saline

6.10.00038

0.471.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●

●●

●

MKL−1: Saline

3.70.00037

0.51.1e−05

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●

●

●

● ●

●

MKL−1: Saline

3.70.00038

0.481.2e−05

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●

●●

●

●●●

MKL−1: Saline

4.50.00036

0.431.1e−05


14

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●●

●

●

●●

MKL−1: Saline

4.70.00038

0.451.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●

●●

MKL−1: Saline

6.20.00038

0.511.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ●

●

●

●

MKL−1: Saline

4.70.00039

0.421.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

● ●

●●

MKL−1: Saline

3.90.00038

0.581.2e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●● ●● ●● ●● ●● ●● ●● ●● ●● ●●

●● ●●

●●

●●

MKL−1: YM155

3.70.00087

0.6425

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●● ●●

●● ●●

●●

●● ●●●●

●●●● ●●

MKL−1: YM155

5.40.00094

0.3411

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●● ●● ●●●●

●●

●●●●

●●●●

●●

●● ●●●●

MKL−1: YM155

50.0011

0.3512

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●●●● ●●

●● ●● ●● ●● ●●●●

●●

●●

●● ●●

●●

MKL−1: YM155

4.10.0073

0.519


15

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●●●●

●●●● ●●

●● ●● ●● ●●

●● ●● ●●

MKL−1: YM155

5.60.0012

0.230.89

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●●●● ●●●●

●●●●

●●●●

●●●●

●●●●●●

MKL−1: YM155

5.30.0010.38

10

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●● ●● ●● ●●●●

●● ●●●●

●●

●●

●●

●● ●●●● ●●

MKL−1: YM155

4.40.0080.39

17

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

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●●

●●

●●

●● ●● ●●●●

MKL−1: YM155

3.70.00097

0.4216

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●●

●● ●●

●●

●●

●● ●●

●●

●●●● ●●

●●

MKL−1: YM155

4.80.0010.315.9

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●●●● ●● ●● ●● ●●

●● ●● ●●●● ●●

●● ●● ●● ●● ●●

●●

●●

●●

●●

●● ●●

●● ●● ●●●● ●●

MKL−1: YM155

30.0023

0.4230

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●●●● ●●

●●●● ●●

●●●●

●●

●●

●● ●●●●

●● ●●●●

MKL−1: YM155

4.70.00077

0.3113

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●●

●● ●● ●●●●

●●●● ●●

●●

●●●● ●●

MKL−1: YM155

4.40.0012

0.292.3


16

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●●

●● ●●

●● ●● ●● ●● ●●

●●●●

●● ●●●●

●●●● ●●

●● ●●●●

●● ●● ●● ●● ●●

MKL−1: YM155

1.90.2

0.3213

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ●●

●

● ●

●● ●

●

MKL−1: YM155

4.30.0013

0.312.4

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●●

●

●

● ●

●●

●

MKL−1: YM155

3.50.0013

0.394.8

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

● ●

●

●●

●● ●

MKL−1: YM155

4.30.0012

0.331.8

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ●

●

●

●

●●

● ●

MKL−1: YM155

2.60.0012

0.392.4

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●

● ●●

● ●

MKL−1: YM155

4.50.0012

0.40.63

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●

●

● ●

●

● ●

●

MKL−1: YM155

3.70.0012

0.410.93

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●

● ● ●

●●

●●

● ●●●

MKL−1: YM155

3.90.0011

0.32


17

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●●

●

●

● ●

●

● ●●

MKL−1: YM155

50.0015

0.347.5

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

● ● ● ● ● ● ●

●

●

●

●

●

● ● ● ● ● ● ●

MKL−1: YM155

2.30.0012

0.7321

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●●

●● ●

●

●●●

MKL−1: YM155

50.0011

0.336

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ●

●

●● ● ● ●

● ●●

●

MS−1: Saline

5.70.00053

0.212.1e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

● ●

●

●

● ● ●● ●

●●●

MS−1: Saline

3.20.00053

0.232.1e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●●

●

●●

● ● ● ●● ●

● ●

MS−1: Saline

4.90.00052

0.22e−05

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●●

●●

●

● ●●

● ●●

● ●

MS−1: Saline

50.00057

0.212.1e−05

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

● ●

●

●

●

●

●

●● ● ● ●

●● ●

●●

MS−1: Saline

3.30.00054

0.192.1e−05


18

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ●

● ● ●●

● ● ● ●

●●

MS−1: YM155

60.00051

0.185.3e−06

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

● ●

●●

●● ●

● ● ● ●● ●

●●

MS−1: YM155

5.10.00049

0.175.2e−06

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ●

● ●

●

●●

● ●●

● ● ●●

● ●●

MS−1: YM155

30.00049

0.25.3e−06

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●● ● ●

●

●●

●

● ● ●● ●

● ● ●●

MS−1: YM155

4.50.00048

0.165.4e−06

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ●

●

●●

● ● ● ●

● ●● ●●

MS−1: YM155

3.95e−04

0.215.2e−06

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ●

●

●●

● ● ● ●

● ●● ●●

MS−1: YM155

3.90.00049

0.215.3e−06

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

●

● ● ●●

● ●● ●

● ●●

●

●● ●

● ●

UISO: Saline

2.50.00056

0.191.6e−05

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

● ● ●

● ●

●●

●

●●

● ●

●●

● ● ●●

UISO: Saline

1.40.00056

0.211.6e−05


19

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ● ●

● ● ● ● ● ●

● ●

●

●

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● ● ● ●

● ●

UISO: Saline

0.990.00055

0.141.6e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ● ●

●

● ●

●

●●

●

●

● ●● ● ● ●

● ● ●

UISO: Saline

2.20.00057

0.181.6e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

● ●

●●

●●

●● ● ●

● ●●

●

UISO: Saline

3.90.00059

0.221.5e−05

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

●

●

●

●

●

●● ● ●

● ●

●

● ●

●●

●●

●

● ● ●

●

UISO: YM155

2.62e−04

0.214

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ● ● ●

● ●

●

●

●

●●

●

●● ● ●

●● ●

● ● ●●

UISO: YM155

2.40.00018

0.2218

0 10 20 30 40 50

05

1015

Day

log 2

(Vol

ume)

● ● ● ●

●●

● ● ●● ●

●

● ● ●●

●●

● ● ●

UISO: YM155

2.12e−04

0.2412

0 10 20 30 40 50

05

1015

log 2

(Vol

ume)

● ● ●

● ●●

●

● ●

●

●●

●

●

● ●●

●●

● ●

UISO: YM155

2.50.00018

0.2519

0 10 20 30 40 50

05

1015

log 2

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ume)

●●

●

●

● ●● ●●

●

●

● ●●

●●●

UISO: YM155

2.20.00021

0.236


20

References

[1] Zhao L, Morgan M, Parsels L, Maybaum J, Lawrence T, Normolle D. (2011) Bayesian Hier-archical Changepoint Methods in Modeling the Tumor Growth Profiles in Xenograft Experi-ments. Clinical Cancer Research 17(5): 1057-64. PMID: 21131555.

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supplementary materials for...mkl-1 rl pant1 uiso rl pant1 survivin α!tubulin figure s1. mcv small...

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