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G Protein-Coupled Receptors
GPCR Products by Class• Class A: Rhodopsin-like• Class B: Secretin-like• Class C: Glutamate• Class F: Frizzled• GPCR Signaling
Opium PoppyPapaver somniferumA source of Morphine
Product Listing | Edition 1 | Euro
Tocris Product Listing Series
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ContentsThis listing contains over 450 products, including agonists, antagonists and allosteric modulators for a wide range of G protein-coupled receptors (GPCRs). GPCRs are divided into their respective classes: Rhodopsin-like (class A), Secretin-like (class B), Glutamate (class C) and Frizzled (class F). Products for GPCR signaling are also listed.
Class A: Rhodopsin-like 4
Class A1/A2 4CCChemokineReceptorsCXCChemokineReceptors
GPCR Crystal Structures 5
Class A2 6Estrogen(GPER)Receptors
Class A3 6AngiotensinReceptorsApelinReceptorsBradykininReceptors
Class A4 6OpioidReceptorsNeuropeptideW/BReceptorsSomatostatinReceptors
Class A5 7GalaninReceptorsKisspeptinReceptorsLeukotrieneReceptorsMelanin-concentratingHormone(MCH)ReceptorsUrotensin-IIReceptors
Class A6 8CholecystokininReceptorsGnRHReceptorGPR103OrexinReceptorsOxytocinReceptorVasopressinReceptors
Class A7 9BombesinReceptorsEndothelinReceptorsGhrelinReceptorMotilinReceptorNeuromedinUReceptorsNeurotensinReceptorsThyrotropin-ReleasingHormoneReceptors
Class A8 10FormylPeptideReceptors
Class A9 10MelatoninReceptorsNeuropeptideYReceptorsTachykininReceptors
Class A11 11FreeFattyAcidReceptorsHydroxycarboxylicAcidReceptors
Class A11/12 11PurinergicReceptors
Class A12 12Platelet-activatingFactorReceptor
Class A13 12CannabinoidReceptorsMelanocortinReceptorsSphingosine-1-phosphateReceptors
Class A13/15 13LysophosphatidicAcidReceptors
Class A14 14ProstanoidReceptorsThromboxane(TP)Receptors
Class A15 14GPR35Protease-activatedReceptors
Class A17 15AdrenergicReceptorsDopamineReceptorsTraceAmine1Receptor
Class A17/18 17HistamineReceptors
Class A17/19 185-HTReceptors
Class A18 19AdenosineReceptorsAcetylcholineMuscarinicReceptors
Other GPCRs 21NeuropeptideFF/AFReceptorsOrphanGPCRsSensoryNeuron-specificReceptors
DREADD Ligands 21
Class B: Secretin-like 22
CalcitoninandRelatedReceptorsCorticotropin-releasingFactorReceptorsGIPReceptorGlucagonReceptorGlucagon-LikePeptideReceptorsPACAPReceptorParathyroidHormoneReceptorsSecretinReceptorVIPReceptors
Class C: Glutamate 24
Calcium-sensingReceptorGABABReceptorsGlutamate(Metabotropic)Receptors
GPCR Allostery 27
Class F: Frizzled 28
SmoothenedReceptor
GPCR Signaling 29
AdenylylCyclasecAMPGProtein(Heterotrimeric)GRKIP3ReceptorPhospholipases
Bias Signaling 30
ReferencesandFurtherReading 31
GPCR ReSeaRCh
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IntroductionGPCRs are transmembrane receptors that mediate signal transduction from the cytosol to the cell interior. There are approximately 850 known GPCRs, which make up the largest receptor superfamily. GPCRs can be classified according to their structural and functional relationship, as represented by the ‘GPCR Tree’.
GPCR Tree Gene AbbreviationsADORA, adenosine receptor; ADR, adrenergic receptor; AGTR, angiotensin receptor; AGTRL1, apelin receptor; AVPR, vasopressin receptor; BDKRB, bradykinin receptor; BRS3, bombesin-like receptor 3; CALCR, calcitonin receptor; CASR, calcium sensing receptor; CCKR, cholecystokinin receptor; CCR, CC chemokine receptor; CHRM, acetylcholine muscarinic receptor; CNR, cannabinoid receptor; CRHR, corticotropin-releasing factor receptor; CXCR, CXC chemokine receptor; CYSLTR, cysteinyl leukotriene receptor; DRD, dopamine receptor; EBI2, eBV-induced G-protein coupled receptor 2; S1PR, sphingosine-1-phosphate receptor; EDNR, endothelin receptor; FPR, formyl peptide receptor; GABBR, GaBaB receptor; GALR, galanin receptor; GCGR, glucagon receptor; GHSR, ghrelin receptor; GIPR, GIP receptor; GLPR, glucagon-like receptor; GNRHR, gonadotropin-releasing hormone receptor; GPR, G-protein coupled receptor; GRM, glutamate receptor metabotropic; GRPR, gastrin-releasing peptide receptor; HCRTR, orexin receptor; HRH, histamine receptor; HTR, 5-hT receptor; LPAR, lysophosphatidic acid receptor; MCR, melanocortin receptor; MCHR, melanin-concentrating hormone receptor; MRGX1 (SNSR1), sensory neuron-specific receptor; MLNR, motilin receptor; MLNR, melatonin receptor; NMBR, neuromedin receptor; NMUR, neuromedin U receptor; NPFFR, neuropeptide FF receptor; NPYR, neuropeptide Y receptor; NTSR, neurotensin receptor; OPR, opioid receptor, OXTR, oxytocin receptor; P2YR, purinergic receptor; PACAPR, pituitary adenylate cyclase-activating polypeptide; PAR, protease-activated receptor; PTAFR, platelet-activating factor receptor; PTGER, prostaglandin e2 receptor; PTGFR, prostaglandin F2 receptor; PTGIR; prostacyclin receptor; PTHR, parathyroid hormone receptor; SCTR, secretin receptor; SMOH, smoothened receptor; SSTR, somatostatin receptor; TACR; tachykinin receptor; TAR1, trace amine 1 receptor; TBXA2R, thromboxane a2 receptor; TRHR, thyrotropin-releasing hormone receptor; UR2R, urotensin receptor; VIPR, vasoactive intestinal peptide
A Representation of the GPCR Tree Featuring Genes of GPCRs Targeted by Tocris Products
ADRA2
CHRM1CHRM1
CHRM1
CHRM1
CHRM1
DRD2
DRD3DRD4
TBXA2R
ADRA1
HTR2ADRB1
DRD5
MLNR
DRD1
ADRB2
ADRB3
S1PR LPAR
CNR1 CNR2
MCR
ADORA2B
ADORA2A
ADORA3 ADORA1
EDNRB
EDNRA
BRS3 GRPR
NMBR
HCRTR1
HCRTR
CCKAR
CCKBR
NPFFR TACR2
TACR1
TACR3NPYR
NTSR
NMUR
MTLR
GHSR
GHRHR
GABBR
CASR
GRM1GRM5
GRM3
GRM2
GRM6GRM4
GRM7GRM8
CALCR
SMOH
SCTR
VIPRCRH1
CRH1PTHR
PACAPR
GLPR
GIPR
GCGR
OXTR
AVPR
GNR
HTR7
HTR6
HTR4
TAR1
PTGFR
PTGER1
PTGIR
CYSLTR
AGTRL1
FPR1
BLTR
BDKBR
AGTR1CCR
CXCRGPR7
OPRL
OPRK
OPRM
OPRD
GALR
MCHR
UR2R
SSTRGPR54
GPR17
P2YR
GPR55
GPR35
PAR
GPR103 PTAFR EBI2 TRHR
MRGX1 (SNSR1)
HRH4 HRH3
HRH2 HRH1
HTR5
HTR1 Class A – Rhodopsin-like
Class B – Secretin-like
Class C – Glutamate
Class F – Frizzled
adapted from Raymond et al (2013) Nat.Rev.Drug Discov. 12 25.
Tocris Product Listing Series
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Class a: Rhodopsin-likeThe Rhodopsin-like receptors are the largest class within the GPCR superfamily, being characterized by certain conserved amino acid residues in their transmembrane helices. Class A receptors have a wide variety of ligands including, neurotransmitters, peptides, glycoproteins, steroid hormones and lipids.
CXCR4 in Complex with IT1t Crystal Structure of the CXCR4 Homodimer in Complex with the CXCR4 Antagonist IT1t
Image adapted from the RSCB PDB (www.rcsb.org) of PDB ID: 3Oe9 Wu et al (2010) Science 330 1066. PMID 20929726.
•IT1tbindstopartofthebindingcavityofCXCR4andinteractswithsidechainsfromhelicesI,II,IIIandVII
•IT1tisapotentCXCR4antagonist(IC50=1.1nM)
•Thecompoundisorallyavailable
Cat. No. 4596
CXCR4 – IT1t
NN
S
SN
NH
B2-Adrenergic – ICI 118,551
NHHO
O
A2A – ZM 241385
OH
NH
N
N N
N
NO
NH2
D3 – Eticlopride
H1 – Doxepin
O
N
CRF1R – CP-376395
N
O NH
3212
4596 0508
0821
1036MGLUR1 – LY 341495
O
CO2HH2N
OHO
1209
1847
N NH
O HO
OCl
Class A1/A2: CC Chemokine Receptors
Antagonists 3129 BMS CCR2 22 high affinity, potent CCR2 antagonist 1 mg
10 mg
50 mg
125
245
980
2595 J 113863 Potent CCR1 antagonist 1 mg
10 mg
50 mg
100
195
760
5176 JNJ 27141491 Potent and selective human CCR2 antagonist 10 mg
50 mg
225
900
3756 Maraviroc Selective CCR5 antagonist 10 mg
50 mg
215
865
2089 RS 102895 CCR2b antagonist 10 mg
50 mg
145
530
2517 RS 504393 highly selective CCR2 antagonist 10 mg 195
3650 SB 328437 Potent and selective CCR3 antagonist 10 mg
50 mg
165
635
CXC Chemokine Receptors
Agonists 4780 VUF 11207 Potent CXCR7 (aCKR3) agonist 10 mg
50 mg
195
775
5668 VUF 11222 high affinity non-peptide CXCR3 agonist 10 mg
50 mg
145
560
Antagonists 3299 aMD 3100 highly selective CXCR4 antagonist 10 mg
50 mg
145
545
4179 aMD 3465 Potent, selective CXCR4 antagonist 10 mg
50 mg
195
760
4487 (±)-aMG 487 CXCR3 antagonist; inhibits cell migration and metastasis 10 mg
50 mg
225
900
5130 CTCe 9908 CXCR4 antagonist; antitumor 1 mg 210
4596 IT1t Potent CXCR4 antagonist 10 mg
50 mg
175
665
Category Cat. No. Product Name Description Unit Size Euro
GPCR ReSeaRCh
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Class a: Rhodopsin-like – continued
GPCR Crystal StructuresCrystallography refers to the study of atomic and molecular structure. The elucidation of molecular structures of membrane proteins such as GPCRs has proven problematic, and only a small fraction of known GPCRs have been solved to date. GPCR crystal structures are invaluable for structure-based drug discovery approaches.
GPCR Crystal Structures and Drug Discovery:
The solving of GPCR crystal structures has been notoriously difficult, due to their flexible conformations. For their structure to be solved GPCRs need to be embedded in a membrane-like environment to maintain their structural integrity. This was difficult to achieve until the last decade, when certain mutations were found to increase GPCR stability and expression levels, while stabilization antibodies can also enhance GPCR stability.
The first GPCR structure to be crystallized was the Rhodopsin receptor in 2000, and receptor stabilization techniques resulted in the discovery of the adenosine a2a receptor and adrenergic β1 and β2 receptors in 2008. To date 26 GPCR structures have been solved (see table below). GPCR crystal structures could prove to be essential for next generation drug discovery. These structures can be utilized by automated computational screens for the identification of novel ligands and chemotypes, which could produce lead compounds for the synthesis of next generation drugs and enhanced therapeutics.
GPCR Crystal Structure Table
Table listing GPCRs whose crystal structures have been solved to date. Where the structure has been solved in complex with a ligand, the ligand is also listed. Ligands in bold are available from Tocris. The PDB-ID is the crystal structures PDB-ID from the RCSB PDB (www.rcsb.org/pdb). Data from zhanglab.ccmb.med.umich.edu/GPCR-eXP.
GPCR Species Ligand PDB-ID Reference
acetylcholine Muscarinic M2 Receptor human Iperoxo 4MQS Kruse et al (2013) Nature 504 101
acetylcholine Muscarinic M3 Receptor Rat Tiotropium (#5902) 4U15 Thorsen et al (2014) Structure 22 1657
adenosine a2a Receptor human
Adenosine (#3624) 2YDO Jaakola et al (2008) Science 322 1211
NECA (#1691) 2YDVLebon et al (2011) Nature 474 521
ZM 241385 (#1036) 3eML
adrenergic β1 Receptor Turkey
Cyanopindolol (#0993) 2VT4
Warne et al (2008) Nature 454 486Dobutamine (#0515) 2Y00
Isoprenaline (#1747) 2Y03
Salbutamol (#0634) 2Y04
adrenergic β2 Receptor humanICI 118,551 (#0821) 3NY8 Wacker et al (2010) J.Am.Chem.Soc 132 11443
Timolol (#0649) 3D4S hanson et al (2008) Structure 16 897
Chemokine CCR5 Receptor Maraviroc (#3756) 4MBS Tan et al (2013) Science 341 1387
Chemokine CXCR1 Receptor human - 2LNL Park et al (2012) Nature 491 779
Chemokine CXCR4 Receptor human IT1t (#4596) 3Oe6 Wu et al (2010) Science 330 1066
Corticotropin-releasing Factor Receptor 1 CP 376395 (#3212) 4K5Y hollenstein et al (2013) Nature 499 438
Dopamine D3 Receptor human Eticlopride (#1847) 3PBL Chien et al (2010) Science 330 1091
Free Fatty acid Receptor 1 TaK-875 4PhU Srivastava et al (2014) Nature 513 124
Glucagon Receptor human - 4L6R Siu et al (2013) Nature 499 444
histamine h1 Receptor human Doxepin (#0508) 3RZe Shimamura et al (2011) Nature 475 65
5-hT1B Dihydroergotamine (#0475) 4IaQ Wang et al (2013) Science 340 610
5-hT2B ergotamine 4IB4 Wacker et al (2013) Science 340 615
Metabotropic Glutamate Receptor 1 LY 341495 (#1209) 3KS9 Dobrovetsky et al (Data yet to be published)
Neurotensin Receptor Neurotensin (#1909) 4GRV White et al (2012) Nature 490 508
κ Opioid Receptor human JDTic 4DJh Wu et al (2012) Nature 485 327
μ Opioid Receptor β-Funaltrexamine (#0926) 4DKL Manglik et al (2012) Nature 485 321
δ Opioid Receptor Naltrindole (#0740) 4eJ4 Granier et al (2012) Nature 485 400
OX2 Orexin Receptor human Suvorexant 4S0V Yin et al (2015) Nature 519 247
Protease-activated Receptor 1 human Vorapaxar 3VW7 Zhang et al (2012) Nature 492 387
Purinergic P2Y12 Receptor 2MeSADP (#1624) 4PXZ Zhang et al (2014) Nature 509 119
Rhodopsin Receptor Bovine 11-cis-Retinal 1F88 Palczewski et al (2000) Science 289 739
Smoothened Receptor humanCyclopamine (#1623) 4O9R Wang et al (2014) Nat.Commun. 5 4355
SANT-1 (#1974) 4N4W Weierstall et al (2014) Nat.Commun. 5 3309
Sphingosine-1 Phosphate Receptor ML 056 (3602) 3V2W hanson et al (2012) Science 335 851
Tocris Product Listing Series
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Category Cat. No. Product Name Description Unit Size Euro
4528 (±)-NBI 74330 Potent and selective CXCR3 antagonist 10 mg 255
5660 NVP CXCR2 20 Potent and selective CXCR2 antagonist 10 mg
50 mg
145
560
2725 SB 225002 Potent and selective CXCR2 antagonist 10 mg
50 mg
180
720
2724 SB 265610 Potent CXCR2 antagonist 1 mg
10 mg
50 mg
100
195
760
4300 TC 14012 CXCR4 antagonist; also CXCR7 (aCKR3) agonist 1 mg 215
Class A2 Estrogen (GPER) Receptors
Agonists 3577 G-1 Potent and selective GPeR agonist 10 mg
50 mg
180
720
1047 ICI 182,780 high affinity GPeR agonist 1 mg
10 mg
50 mg
100
195
760
Antagonists 3678 G-15 high affinity and selective GPeR antagonist 10 mg
50 mg
180
720
Class A3 Angiotensin Receptors
Agonists 1158 angiotensin II Potent vasoconstrictor peptide 5 mg 125
5728 eXP 3174 Potent and selective aT1 antagonist 10 mg
50 mg
130
485
Antagonists 5798 Irbesartan Potent aT1 antagonist 50 mg 100
3798 Losartan potassium Selective, non-peptide aT1 antagonist 50 mg 110
1361 PD 123319 Potent, selective non-peptide aT2 antagonist 10 mg
50 mg
195
760
Apelin (APJ) Receptors
Agonists 2420 [Pyr1]-apelin-13 Potent peptide agonist for aPJ receptor 1 mg 175
3007 apelin-17 (human, bovine) endogenous aPJ receptor agonist 1 mg 225
2426 apelin-36 (human) endogenous aPJ receptor agonist 1 mg 400
Antagonists 4748 ML 221 aPJ receptor antagonist 10 mg
50 mg
180
720
Bradykinin Receptors
Agonists 3004 Bradykinin endogenous agonist at bradykinin receptors (B2 > B1) 5 mg 85
Antagonists 3014 hOe 140 Potent and selective B2 antagonist 500 µg 195
Class A4 δ Opioid Receptor
Agonists 0764 SNC 80 highly selective non-peptide δ agonist 10 mg
50 mg
195
760
Antagonists 0740 Naltrindole Selective non-peptide δ antagonist 10 mg
50 mg
145
520
κ Opioid Receptor
Agonists 3195 Dynorphin a endogenous κ agonist 1 mg 200
5519 (-)-Pentazocine κ agonist; antinociceptive 10 mg 100
0496 (-)-U-50488 Standard selective κ agonist; more active enantiomer of (±)-U-50488 (Cat. No. 0495)
10 mg
50 mg
145
560
0495 (±)-U-50488 Standard selective κ agonist 25 mg 145
Antagonists 0347 nor-Binaltorphimine Standard selective κ antagonist 10 mg
50 mg
160
600
GPCR ReSeaRCh
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Class a: Rhodopsin-like – continued
μ Opioid Receptor
Agonists 1171 DaMGO Selective μ agonist 1 mg 80
Antagonists 1560 CTaP Selective and potent μ antagonist 1 mg 145
2601 Cyprodime Selective μ antagonist 10 mg 195
0926 β-Funaltrexamine Irreversible μ-selective antagonist 10 mg
50 mg
195
760
Opioid Receptors (Non-selective)
Agonists 5158 Morphine Narcotic opioid analgesic 50 mg 100
1419 Naloxone benzoylhydrazone Full κ agonist; partial μ and δ agonist 10 mg
50 mg
125
445
Antagonists 0599 Naloxone Broad spectrum opioid receptor antagonist 100 mg 100
0677 Naltrexone Broad spectrum opioid receptor antagonist 100 mg 100
Neuropeptide W/B Receptors
Agonists 3009 Neuropeptide W-23 (human) endogenous NPBW1 and NPBW2 agonist 1 mg 245
Antagonists 4948 CYM 50769 Novel non-peptide NPBWR1 antagonist 10 mg
50 mg
180
720
Somatostatin (sst) Receptors
Agonists 1979 L-803,087 Potent and selective sst4 agonist 10 mg 270
1818 Octreotide sst2, sst3 and sst5 agonist 1 mg 245
1157 Somatostatin Influences growth hormone release 1 mg 110
Antagonists 3493 Cyclosomatostatin Non-selective sst receptor antagonist 1 mg 175
1843 CYN 154806 Selective sst2 antagonist 1 mg 225
Class A5 Galanin Receptors
Agonists 2696 Galanin (1-29) (rat, mouse) Non-selective galanin receptor agonist 1 mg 200
1179 Galanin (1-30) (human) endogenous galanin receptor agonist 200 µg 180
Kisspeptin Receptor
Agonists 2570 Kisspeptin 10 (human) endogenous kisspeptin receptor ligand 1 mg 275
4243 Kisspeptin 10 (rat) endogenous kisspeptin receptor ligand 1 mg 160
Leukotriene Receptors
Agonists 2307 Leukotriene B4 BLT1/BLT2 receptor agonist and potent chemotactic factor 50 µg 325
Antagonists 2338 MK 571 Potent CysLT1 (LTD4) inverse agonist; also MRP1 inhibitor 10 mg 175
Other 1311 MK 886 Inhibitor of 5-lipoxygenase-activating protein (FLaP) 10 mg
50 mg
180
720
Melanin-concentrating Hormone (MCH) Receptors
Agonists 3806 MCh (human, mouse, rat) Potent endogenous MCh receptor agonist 100 µg 85
Antagonists 4242 GW 803430 MCh1 antagonist 10 mg
50 mg
215
865
4365 TC-MCh 7c Selective MCh1 antagonist 10 mg 245
Urotensin-II (UT) Receptor
Agonists 2484 (±)-aC 7954 Non-peptide UT receptor agonist 10 mg
50 mg
180
720
1642 Urotensin II (human) endogenous vasoactive agonist for the UT receptor 1 mg 245
Antagonists 5110 GSK 1562590 high affinity, selective UT receptor antagonist 10 mg
50 mg
245
980
3571 SB 657510 Selective UT receptor antagonist 10 mg
50 mg
190
740
4667 SB 706375 high affinity, non-peptide UT receptor antagonist 10 mg
50 mg
180
720
Category Cat. No. Product Name Description Unit Size Euro
Tocris Product Listing Series
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Orexin Receptors
ACT 462206 (5319)Potent, dual orexin receptor antagonist
EMPA (4558)Highly potent and selective OX2
antagonist; brain penetrant
SB 674042 (4673)Potent and selective non-peptide OX1 antagonist
IPSU (5645)OX2 antagonist; orally bioavailable
and brain penetrant
HN
O
N
SO
O
O
N
N
O
NS
N
OMe
O O
N
O
O
NN
S
N
F
N
NO N
N
O
NH
Featured Orexin Receptor Antagonists
Category Cat. No. Product Name Description Unit Size Euro
Class A6 Cholecystokinin (CCK) Receptors
Agonists 2411 a-71623 Potent and selective CCK1 agonist; suppresses feeding 1 mg 255
1166 CCK Octapeptide, sulfated C-terminal octapeptide of CCK 1 mg 245
3006 Gastrin I (human) Selective CCK2 agonist 1 mg 275
Antagonists 2607 CI 988 Potent and selective CCK2 antagonist 10 mg
50 mg
255
1015
2304 Devazepide Selective CCK1 antagonist; orally active 10 mg
50 mg
225
900
Gonadotropin-releasing Hormone (GnRH) Receptor
Agonists 3592 Goserelin GnRh receptor agonist 10 mg 160
Antagonists 3536 Cetrorelix Potent GnRh receptor antagonist 1 mg 195
2519 T 98475 GnRh receptor antagonist 1 mg 215
GPR103
Ligands 4402 26RFa Ligand of GPR103; orexigenic neuropeptide 1 mg 195
Orexin Receptors
Agonists 1455 Orexin a (human, rat, mouse) endogenous agonist at OX1 and OX2 500 µg 445
2142 [ala11,D-Leu15]-Orexin B Potent, selective OX2 receptor agonist 1 mg 305
1456 Orexin B (human) endogenous agonist at OX1 and OX2 500 µg 270
1457 Orexin B (mouse) endogenous agonist at OX1 and OX2 500 µg 270
Antagonists 4983 aCT 335827 Potent and selective OX1 antagonist 10 mg
50 mg
290
1170
5319 aCT 462206 Potent, dual orexin receptor antagonist 10 mg
50 mg
200
795
4558 eMPa highly potent and selective OX2 antagonist; brain penetrant 10 mg
50 mg
210
820
5645 IPSU OX2 receptor antagonist; orally bioavailable and brain penetrant 10 mg 195
4317 JNJ 10397049 Selective OX2 receptor antagonist 10 mg
50 mg
195
760
GPCR ReSeaRCh
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Potent and Selective Motilin Receptor Antagonist
MA 2029 Cat. No. 4934
MA2029isapotentandselectivemotilinreceptorantagonist(IC50=4.9nM)thatexhibitsselectivityforthemotilinreceptoroverarangeofotherreceptorsandionchannels.Thecompoundinhibitsmotilin-inducedcolonicandabdominalcontractionsin vivo.MA2029isalsoorallyactive.
JNJ 27141491 (Cat. No. 5176)
N
F
F NHS
OOMe
O N
ML 00253764 (4854)
Br
OMe
F
NHN
TC-G 1008 (5355)
BIBN 4096 (4561)
N
N
N
NH
NH
Cl
NH
SOO
NHN
N
HNO
O
HN
N N NO O
NH2
Br
Br
HO
Purmorphamine (4551)
N
N N
N
NH
O
N
O
CMPD101 (5642)
N
N N
NNH
O
HN
F3C
MA 2029 (4934)
F
N
O
NH
ONHO
HN
OH
Class a: Rhodopsin-like – continued
Category Cat. No. Product Name Description Unit Size Euro
1960 SB 334867 Selective non-peptide OX1 antagonist 1 mg
10 mg
50 mg
100
195
760
4673 SB 674042 Potent and selective non-peptide OX1 antagonist 10 mg
50 mg
285
1130
3371 TCS OX2 29 Potent and selective OX2 antagonist 10 mg
50 mg
195
760
Oxytocin Receptor
Agonists 1910 Oxytocin endogenous oxytocin receptor agonist 1 mg 80
3933 WaY 267464 Potent non-peptide oxytocin receptor agonist 10 mg 240
Antagonists 2641 L-368,899 Potent, non-peptide oxytocin receptor antagonist 1 mg
10 mg
145
285
2410 L-371,257 Potent and selective oxytocin receptor antagonist 10 mg 215
Vasopressin Receptors
Antagonists 2310 SR 49059 Selective, orally active V1a receptor antagonist 10 mg 305
5181 Tolvaptan Potent and selective V2 receptor antagonist; renoprotective and orally active
10 mg
50 mg
160
600
Class A7 Bombesin Receptors
Agonists 5600 Ba 1 Potent BRS-3 agonist; also NMBR and GRPR agonist 1 mg 195
1789 GRP (human) endogenous GRP receptor agonist 1 mg 245
Antagonists 5599 ML 18 BRS-3 antagonist; also GRPR agonist 10 mg 255
Endothelin (ET) Receptors
Agonists 1189 BQ-3020 Selective eTB agonist 500 µg 215
1160 endothelin 1 (human, porcine) endogenous endothelin receptor agonist 100 µg 180
Antagonists 1188 BQ-123 Selective eTa antagonist 500 µg 175
1500 BQ 788 sodium salt Selective eTB antagonist 1 mg 290
1838 IRL-2500 Potent eTB antagonist 10 mg 240
Ghrelin Receptor
Agonists 1463 Ghrelin (human) endogenous ghrelin receptor agonist 1 mg 370
1465 Ghrelin (rat) endogenous ghrelin receptor agonist 1 mg 405
5272 MK 0677 high affinity ghrelin receptor agonist 10 mg
50 mg
145
560
Antagonists 1922 [D-Lys3]-GhRP-6 Ghrelin receptor antagonist 5 mg 140
3959 YIL 781 Ghrelin receptor (GhS-R1a) antagonist 10 mg
50 mg
200
795
Motilin Receptor
Agonists 2264 Motilin (human, porcine) endogenous motilin receptor agonist 1 mg 275
Antagonists 5074 aNQ 11125 Selective motilin receptor antagonist 1 mg 180
4934 Ma 2029 Potent and selective motilin receptor antagonist; orally active
10 mg
50 mg
210
820
Tocris Product Listing Series
10 |
Neuromedin U (NMU) Receptors
Agonists 3648 Neuromedin S (rat) Potent, endogenous NMU1 and NMU2 agonist 500 µg 285
1917 Neuromedin U (rat) endogenous modulator of blood pressure and flow, gut ion transport, feeding and body temperature
1 mg 200
Neurotensin (NTS) Receptors
Agonists 1909 Neurotensin endogenous neurotensin receptor agonist 1 mg 80
5087 TC NTR1 17 Selective non-peptide NTS1 agonist 10 mg
50 mg
225
900
Antagonists 2309 SR 142948 highly potent NT receptor antagonist 1 mg
10 mg
130
255
3721 SR 48692 Selective non-peptide NTS1 antagonist 10 mg
50 mg
245
980
Thyrotropin-Releasing Hormone Receptors
Agonists 2672 Taltirelin Synthetic thyrotropin-releasing hormone analog 1 mg
10 mg
115
215
Class A8 Formyl Peptide Receptors (FPRs)
Agonists 5583 Quin C1 Potent and selective FPR2 agonist 10 mg
50 mg
175
680
4624 TC-FPR 43 Potent FPR2 agonist 10 mg
50 mg
175
680
Antagonists 2262 WRW4 Selective FPR2 antagonist 1 mg 100
Class A9 Melatonin (MT) Receptors
Agonists 0737 2-Iodomelatonin high affinity melatonin receptor agonist 10 mg
50 mg
80
245
0680 2-Phenylmelatonin Potent melatonin receptor agonist 10 mg
50 mg
140
505
Antagonists 0877 Luzindole MT1/MT2 antagonist 10 mg
50 mg
145
560
1034 4-P-PDOT MT2 antagonist 10 mg
50 mg
145
530
Neuropeptide Y (NPY) Receptors
Agonists 1153 Neuropeptide Y (human, rat) endogenous NPY receptor agonist 200 µg 145
Antagonists 2412 BIBO 3304 highly selective NPY Y1 receptor antagonist 10 mg
50 mg
285
1130
2707 BIBP 3226 Mixed NPY Y1 and NPFF receptor antagonist 1 mg
10 mg
140
270
1700 BIIe 0246 Potent, selective non-peptide NPY Y2 receptor antagonist 1 mg
10 mg
145
290
4018 JNJ 5207787 Selective NPY Y2 receptor antagonist 10 mg
50 mg
240
935
Tachykinin (NK) Receptors
Agonists 1668 GR 64349 Potent, selective NK2 agonist 1 mg 325
1669 GR 73632 Potent, selective NK1 agonist 1 mg 305
1068 Senktide Tachykinin NK3 agonist 500 µg 125
Antagonists 1274 GR 159897 Non-peptide, potent NK2 antagonist 10 mg
50 mg
195
760
1145 L-733,060 Potent NK1 antagonist 10 mg
50 mg
195
760
1635 RP 67580 Potent and selective NK1 antagonist 10 mg
50 mg
195
760
4672 SB 223412 Potent, selective non-peptide NK3 antagonist; brain penetrant 10 mg
50 mg
180
705
Category Cat. No. Product Name Description Unit Size Euro
GPCR ReSeaRCh
tocris.com | 11
Class a: Rhodopsin-like – continued
Free Fatty Acid Receptors
O
SNH
O OO
CO2H
FO
HNS
O
O
GSK 137647 (5257)Potent and selective FFA4 (GPR120) agonist
TUG 891 (4601)Potent and selective FFA4
(GPR120) agonist
AH 7614 (5256)Selective FFA4 (GPR120) antagonist
Featured Free Fatty Acid Receptor Agonists and Antagonists
Class A11 Free Fatty Acid (FFA) Receptors
Agonists 5257 GSK 137647 Potent and selective FFa4 (GPR120) agonist 10 mg
50 mg
110
405
4601 TUG 891 Potent and selective FFa4 (GPR120) agonist 10 mg
50 mg
175
635
Antagonists 5256 ah 7614 Selective FFa4 (GPR120) antagonist 10 mg
50 mg
110
405
5357 DC 260126 FFa1 (GPR40) antagonist 10 mg
50 mg
85
310
Hydroxycarboxylic Acid (HCA) Receptors
Agonists 1762 acifran GPR109a (hCa2) and GPR109B agonist; hypolipidemic agent 10 mg
50 mg
145
560
4599 3,5-DhBa Selective hCa1 agonist 50 mg 65
4622 MK 1903 Potent and selective GPR109a (hCa2) agonist 10 mg
50 mg
195
760
Class A11/12 Purinergic (P2Y) Receptors
Agonists 3245 aTP P2 agonist 50 mg 80
3209 α,β-Methyleneadenosine 5ʹ-triphosphate trisodium salt
P2 agonist 10 mg 180
1624 2-Methylthioadenosine diphosphate Potent agonist for P2Y1, P2Y12 and P2Y13 10 mg 270
2157 MRS 2365 highly potent and selective P2Y1 agonist 1 mg 320
2915 MRS 2690 Potent P2Y14 agonist 1 mg 285
2502 MRS 2693 trisodium salt Selective P2Y6 agonist 1 mg 225
3884 MRS 2768 tetrasodium salt Selective P2Y2 agonist 1 mg 285
4261 MRS 4062 Selective P2Y4 agonist 1 mg 255
2715 PSB 0474 Potent and selective P2Y6 agonist 1 mg 285
4333 PSB 1114 Potent, selective P2Y2 agonist 1 mg 285
3280 2-ThioUTP tetrasodium salt Potent and selective P2Y2 agonist 1 mg 290
3279 UTPγS trisodium salt Selective P2Y2/4 agonist 1 mg 200
Antagonists 4890 aR-C 118925XX Selective, competitive P2Y2 antagonist 5 mg 275
3321 aR-C 66096 tetrasodium salt Potent and selective P2Y12 antagonist 1 mg 305
1820 (+)-Clopidogrel Selective P2Y12 antagonist 10 mg
50 mg
180
720
5316 elinogrel P2Y12 antagonist 10 mg
50 mg
195
775
0900 MRS 2179 tetrasodium salt Selective P2Y1 antagonist 10 mg
50 mg
210
820
Category Cat. No. Product Name Description Unit Size Euro
Tocris Product Listing Series
12 |
2402 MRS 2211 Competitive P2Y13 antagonist 10 mg
50 mg
125
445
2158 MRS 2279 Selective, high affinity P2Y1 antagonist 1 mg 320
2159 MRS 2500 extremely potent and selective P2Y1 antagonist 1 mg 305
2146 MRS 2578 Selective P2Y6 antagonist 10 mg
50 mg
125
420
3830 NF 340 Selective P2Y11 antagonist 10 mg 195
3983 PSB 0739 highly potent P2Y12 antagonist 10 mg
50 mg
175
665
Class A12 Platelet-activating Factor (PAF) Receptor
Agonists 3022 edelfosine PaF receptor agonist 10 mg 125
2940 PaF (C16) endogenous PaF receptor agonist 1 mg 65
Antagonists 2339 WeB 2086 Potent PaF receptor antagonist 1 mg
10 mg
125
240
Class A13 Cannabinoid (CB) Receptors
Agonists 2928 CB 13 Potent dual CB1/CB2 agonist 10 mg
50 mg
140
490
2764 GP 1a highly selective CB2 agonist 10 mg
50 mg
215
865
3088 hU 308 Potent and selective CB2 agonist 10 mg
50 mg
245
980
Antagonists 1117 aM 251 Potent CB1 antagonist; also GPR55 agonist 1 mg
10 mg
50 mg
80
160
600
1115 aM 281 Potent, selective CB1 antagonist/inverse agonist 10 mg
50 mg
195
760
1120 aM 630 CB2 selective antagonist/inverse agonist 10 mg
50 mg
195
760
1570 (-)-Cannabidiol Natural cannabinoid; GPR55 antagonist, weak CB1 antagonist and CB2 inverse agonist
10 mg
50 mg
160
600
2479 JTe 907 Selective CB2 receptor antagonist/inverse agonist 10 mg
50 mg
195
760
4605 (±)-SLV 319 Potent and selective CB1 receptor antagonist 10 mg
50 mg
200
795
Modulators 5321 PSNCBaM-1 CB1 receptor negative allosteric modulator 10 mg
50 mg
180
705
Antagonists 0923 SR 141716a Selective CB1 receptor antagonist 10 mg
50 mg
110
405
Other 1445 N-arachidonylglycine endocannabinoid; suppresses pain in vivo 5 mg
25 mg
125
445
2540 Tocrifluor T1117 Novel fluorescent cannabinoid ligand; fluorescent form of aM 251 (Cat. No. 1117)
100 µg 255
Category Cat. No. Product Name Description Unit Size Euro
GPCR ReSeaRCh
tocris.com | 13
Class a: Rhodopsin-like – continued
Melanocortin MC4 Receptor Antagonist
ML 00253764 Cat. No. 4854
ML00253764isanon-peptideMC4receptorantagonist(IC50valuesare320,810and2120nMforMC4,MC3andMC5receptors,respectively).Thecompoundincreasesfoodintakeandreduceslossofleanbodymassintumorbearingmice.ML 00253764isalsobrainpenetrant.
JNJ 27141491 (Cat. No. 5176)
N
F
F NHS
OOMe
O N
ML 00253764 (4854)
Br
OMe
F
NHN
TC-G 1008 (5355)
BIBN 4096 (4561)
N
N
N
NH
NH
Cl
NH
SOO
NHN
N
HNO
O
HN
N N NO O
NH2
Br
Br
HO
Purmorphamine (4551)
N
N N
N
NH
O
N
O
CMPD101 (5642)
N
N N
NNH
O
HN
F3C
MA 2029 (4934)
F
N
O
NH
ONHO
HN
OH
Melanocortin (MC) Receptors
Agonists 3492 aCTh (1-39) Potent endogenous MC2 agonist 1 mg 320
4053 BMS 470539 Potent, selective MC1 receptor agonist 10 mg
50 mg
225
900
3013 [Nle4,D-Phe7]-α-MSh Melanocortin receptor agonist 1 mg 160
3032 ThIQ Potent and selective MC4 receptor agonist 1 mg 215
Antagonists 4854 ML 00253764 Melanocortin MC4 receptor antagonist; brain penetrant 10 mg
50 mg
210
820
4919 PG 106 Selective MC3 receptor antagonist 1 mg 245
Sphingosine-1-phosphate Receptors
Agonists 3601 CYM 5442 Selective S1P1 receptor agonist 10 mg
50 mg
200
795
5418 CYM 5520 Selective S1P2 allosteric agonist 10 mg
50 mg
160
600
4897 CYM 5541 Selective S1P3 receptor allosteric agonist 10 mg
50 mg
160
630
1370 Sphingosine-1-phosphate endogenous agonist at S1P1-5 1 mg 175
Antagonists 4679 CYM 50358 Potent and selective S1P4 antagonist 10 mg
50 mg
210
820
2392 JTe 013 S1P2 receptor antagonist 10 mg 195
5328 TY 52156 S1P3 receptor antagonist 10 mg
50 mg
160
630
4195 VPC 23019 S1P1 and S1P3 antagonist 10 mg 285
3602 W146 Potent and selective S1P1 receptor antagonist 1 mg 155
Class A13/15 Lysophosphatidic Acid (LPA) Receptors
Agonists 4779 GRI 977143 Selective LPa2 non-lipid agonist 10 mg
50 mg
180
720
Antagonists 4878 h2L5186303 Potent and selective LPa2 antagonist 10 mg
50 mg
180
720
5056 Ki 16425 LPa1 and LPa3 antagonist 10 mg
50 mg
165
635
4708 TC LPa5 4 LPa5 antagonist 10 mg
50 mg
195
760
Category Cat. No. Product Name Description Unit Size Euro
Tocris Product Listing Series
14 |
Class A14 Prostanoid Receptors
Agonists 1620 alprostadil Prostaglandin; vasodilator and antiplatelet agent in vivo 10 mg
50 mg
165
635
4180 Beraprost sodium Potent prostacyclin IP receptor agonist 1 mg 110
2295 (±)-Cloprostenol sodium salt Water-soluble PGF2α analog and potent FP receptor agonist 10 mg 360
2038 Iloprost Prostacyclin (PGI2) analog 1 mg 285
2296 Prostaglandin e2 Major endogenous prostanoid 10 mg 145
4214 Prostaglandin F2α Naturally-occurring prostanoid; potent vasoconstrictor 10 mg 215
3351 Selexipag Selective prostacyclin IP1 receptor agonist 10 mg
50 mg
215
865
5349 Treprostinil Potent prostacyclin (PGI2) analog 10 mg 225
Antagonists 2514 L-161,982 Selective eP4 antagonist 10 mg 275
3342 L-798,106 Potent and highly selective eP3 antagonist 10 mg
50 mg
195
760
5406 ONO 8130 eP1 antagonist 10 mg
50 mg
225
900
3565 ONO ae3 208 high affinity and selective eP4 antagonist 10 mg
50 mg
190
740
4818 PF 04418948 Potent and selective eP2 antagonist 10 mg
50 mg
180
720
4268 Ro 1138452 Selective prostacyclin IP antagonist 10 mg
50 mg
190
740
5052 TG 4-155 high affinity and selective eP2 antagonist 10 mg
50 mg
195
760
Thromboxane (TP) Receptors
Agonists 1932 U 46619 Potent, stable thromboxane a2 (TP) receptor agonist 1 mg 145
Antagonists 5568 S 18886 Potent thromboxane a2 (TP) receptor antagonist 10 mg 130
Class A15 GPR35
Agonists 4298 Pamoic acid disodium salt GPR35 agonist 50 mg 100
Antagonists 4293 CID 2745687 GPR35 antagonist 10 mg
50 mg
175
665
4172 ML 145 GPR35 antagonist 10 mg
50 mg
190
740
Protease-activated Receptors (PARs)
Agonists 3015 2-Furoyl-LIGRLO-amide Potent and selective PaR2 agonist 1 mg 125
3010 SLIGKV-Nh2 PaR2 agonist 5 mg 145
1468 SLIGRL-Nh2 PaR2-activating peptide 1 mg 245
1464 TFLLR-Nh2 PaR1-activating peptide 1 mg 255
3497 TRaP-6 PaR1 peptide fragment (residues 42-47); acts as a PaR1 agonist
5 mg 195
Antagonists 4751 FSLLRY-Nh2 PaR2 peptide antagonist 1 mg 100
5387 ML 354 Selective PaR4 antagonist 10 mg
50 mg
140
505
1592 SCh 79797 Potent, selective non-peptide PaR1 antagonist 10 mg
50 mg
215
865
1488 tcY-Nh2 Selective PaR4 antagonist 1 mg 180
Category Cat. No. Product Name Description Unit Size Euro
GPCR ReSeaRCh
tocris.com | 15
Class a: Rhodopsin-like – continued
β2 Adrenergic Receptor in Complex with ICI 118,551 Crystal Structure of the β2 Adrenergic Receptor in Complex with the β2 Antagonist ICI 118,551
Image adapted from the RSCB PDB (www.rcsb.org) of PDB ID: 3NY8 Wacker et al (2010) J.Am.Chem.Soc. 132 11443. PMID 20669948.
• ICI118,551bindstotheorthostericbindingsiteofβ2
• ICI118,551isaselectiveβ2antagonistthatexhibitsselectivityforβ2overβ1andβ3receptors
• Thecompoundisactivein vivo
Cat. No. 0821
CXCR4 – IT1t
NN
S
SN
NH
B2-Adrenergic – ICI 118,551
NHHO
O
A2A – ZM 241385
OH
NH
N
N N
N
NO
NH2
D3 – Eticlopride
H1 – Doxepin
O
N
CRF1R – CP-376395
N
O NH
3212
4596 0508
0821
1036MGLUR1 – LY 341495
O
CO2HH2N
OHO
1209
1847
N NH
O HO
OCl
extracellularMembraneIntracellular
Class A17 α Adrenergic Receptors
Agonists 1052 a 61603 α1a agonist 10 mg
50 mg
175
635
0888 Cirazoline Selective α1 agonist 10 mg 140
2749 Dexmedetomidine Potent, highly selective α2 agonist; active isomer of medetomidine (Cat. No. 5160)
10 mg
50 mg
175
635
0475 Dihydroergotamine Partial α agonist; non-selective 100 mg 110
5169 Noradrenaline endogenous adrenergic hormone and neurotransmitter 50 mg 65
Antagonists 0986 Imiloxan highly selective α2B antagonist 10 mg
50 mg
140
470
β Adrenergic Receptors
Agonists 0948 BRL 37344, sodium salt β3 agonist 10 mg
50 mg
160
600
1499 CL 316243 highly selective β3 agonist 10 mg
50 mg
180
705
0515 Dobutamine β1 and β2 agonist 50 mg 190
1448 Formoterol Potent and selective β2 agonist 10 mg
50 mg
145
545
1747 Isoproterenol Standard selective β agonist 100 mg 100
2197 L-755,507 Very potent and selective β3 partial agonist 10 mg
50 mg
175
665
0634 Salbutamol Non-selective β-adrenergic agonist 250 mg 140
0950 Xamoterol β1 selective partial agonist 10 mg
50 mg
160
600
Antagonists 0906 Betaxolol Selective β1 antagonist 10 mg
50 mg
145
545
2685 Carvedilol β-adrenoceptor and α1-adrenoceptor antagonist 50 mg 100
1024 CGP 20712 highly potent and selective β1 antagonist 10 mg
50 mg
195
760
0993 Cyanopindolol β-adrenergic receptor antagonist; also 5-hT1a/1B antagonist 10 mg
50 mg
145
560
0821 ICI 118,551 Very selective β2 antagonist 10 mg
50 mg
175
635
Category Cat. No. Product Name Description Unit Size Euro
Tocris Product Listing Series
16 |
D3 Dopamine Receptor in Complex with EticloprideCrystal Structure of the D3 Dopamine Receptor in Complex with the D3/D2 Antagonist Eticlopride
Image adapted from the RSCB PDB (www.rcsb.org) of PDB ID: 3PBL Chien et al (2010) Science 330 1091. PMID 21097933.
• EticlopridebindstopartoftheD3bindingpocketdefinedbysidechainsofhelicesIII,V,VIandVII.
• EticloprideisaselectiveD3/D2receptorantagonist(Kivaluesare160and500nM,respectively)
• Thecompoundisanantipsychotic
Cat. No. 1847
CXCR4 – IT1t
NN
S
SN
NH
B2-Adrenergic – ICI 118,551
NHHO
O
A2A – ZM 241385
OH
NH
N
N N
N
NO
NH2
D3 – Eticlopride
H1 – Doxepin
O
N
CRF1R – CP-376395
N
O NH
3212
4596 0508
0821
1036MGLUR1 – LY 341495
O
CO2HH2N
OHO
1209
1847
N NH
O HO
OCl
extracellular
Membrane
Intracellular
2760 L-748,337 Selective β3 antagonist 10 mg
50 mg
175
665
1511 SR 59230a Potent and selective β3 antagonist 10 mg
50 mg
180
720
0649 (S)-Timolol β1 antagonist 100 mg 100
Dopamine D1/D5 Receptors
Agonists 1701 a 77636 Potent, selective D1-like agonist; orally active 10 mg
50 mg
195
760
0884 Dihydrexidine Selective D1-like agonist 5 mg
25 mg
145
560
0922 SKF 38393 Selective D1-like agonist 100 mg 145
1447 SKF 81297 D1 agonist 10 mg
50 mg
195
760
2074 SKF 83959 D1-like partial agonist 10 mg
50 mg
180
695
Antagonists 0925 SCh 23390 Standard selective D1-like antagonist; also 5-hT2C and 5-hT1C agonist
10 mg
50 mg
145
545
2299 SCh 39166 high affinity D1/D5 antagonist 10 mg
50 mg
195
760
1586 SKF 83566 Potent, selective D1-like antagonist 10 mg
50 mg
110
385
Dopamine D2/D3/D4 Receptors
Agonists 4552 a 412997 Selective D4 agonist 10 mg
50 mg
145
520
1243 (+)-PD 128907 D3 agonist (D3 ≥ D2 > D4) 10 mg
50 mg
245
980
1065 PD 168077 high affinity, selective D4 agonist 10 mg
50 mg
160
600
2773 Sumanirole D2-selective agonist 10 mg
50 mg
190
740
Antagonists 1847 eticlopride Selective D2/D3 antagonist 10 mg
50 mg
145
545
1003 L-741,626 high affinity D2 antagonist 10 mg
50 mg
140
500
Category Cat. No. Product Name Description Unit Size Euro
GPCR ReSeaRCh
tocris.com | 17
Class a: Rhodopsin-like – continued
H1 Histamine Receptor in Complex with DoxepinCrystal Structure of the H1 Histamine Receptor in Complex with the H1 Antagonist Doxepin
Image adapted from the RSCB PDB (www.rcsb.org) of PDB ID: 3RZe Shimamura et al (2011) Nature 475 65. PMID 21697825.
• DoxepinbindsdeepintheH1bindingpocketdefinedbysidechainsofhelicesIII,VandVI,andinteractswiththeTrp4286.48residue
• DoxepinisahighaffinityH1receptorantagonist(Kd=310pM)
• Thecompoundisatricyclicantidepressant
Cat. No. 0508
CXCR4 – IT1t
NN
S
SN
NH
B2-Adrenergic – ICI 118,551
NHHO
O
A2A – ZM 241385
OH
NH
N
N N
N
NO
NH2
D3 – Eticlopride
H1 – Doxepin
O
N
CRF1R – CP-376395
N
O NH
3212
4596 0508
0821
1036MGLUR1 – LY 341495
O
CO2HH2N
OHO
1209
1847
N NH
O HO
OCl
extracellularMembraneIntracellular
1004 L-741,742 highly selective D4 antagonist 10 mg
50 mg
145
530
1002 L-745,870 highly selective D4 antagonist 10 mg
50 mg
145
530
4207 SB 277011a Selective D3 antagonist 10 mg
50 mg
175
635
Dopamine Receptors (Non-selective)
Agonists 2073 (R)-(-)-apomorphine Dopamine agonist; non-subtype-selective 50 mg 100
Antagonists 1847 eticlopride Selective D2/D3 antagonist 10 mg
50 mg
145
545
Trace Amine 1 Receptor (TA1)
Agonists 5252 Ractopamine Ta1 agonist 50 mg 55
Antagonists 4518 ePPTB Ta1 antagonist/inverse agonist 10 mg
50 mg
145
560
Class A17/18 Histamine Receptors
Agonists 0646 hTMT h1 / h2 agonist 10 mg
50 mg
145
545
0569 (R)-(-)-α-Methylhistamine Potent, standard h3 agonist 10 mg
50 mg
140
505
2342 4-Methylhistamine Selective, high affinity h4 agonist 10 mg
50 mg
180
720
2478 2-Pyridylethylamine h1 receptor agonist 50 mg 85
Antagonists 3489 astemizole Orally active, potent h1 antagonist; also KV11.1 (heRG) channel blocker
50 mg 80
3743 BF 2649 h3 receptor inverse agonist/antagonist 10 mg
50 mg
145
560
0508 Doxepin highly potent h1 antagonist; also binds to h4 receptor 1 g 80
4021 JNJ 7777120 Selective h4 receptor antagonist 10 mg
50 mg
160
600
0660 Mepyramine Selective h1 inverse agonist 100 mg 80
1070 Zolantidine Potent, centrally active h2 antagonist 10 mg
50 mg
160
600
Category Cat. No. Product Name Description Unit Size Euro
Tocris Product Listing Series
18 |
Class A17/19 5-HT1 Receptors
Agonists 1317 CP 94253 Potent, selective 5-hT1B agonist 10 mg
50 mg
180
665
0529 8-hydroxy-DPaT Selective 5-hT1a agonist; also has moderate affinity for 5-hT7
10 mg
50 mg
80
240
3079 LY 334370 Selective 5-hT1F agonist 10 mg
50 mg
195
760
1985 PNU 142633 highly selective 5-hT1D agonist 10 mg 215
Antagonists 1477 GR 127935 Potent, selective 5-hT1B/1D antagonist 10 mg
50 mg
215
865
1054 GR 55562 5-hT1B antagonist 10 mg
50 mg
175
635
1242 SB 216641 Selective h5-hT1B antagonist 10 mg
50 mg
200
795
1221 SB 224289 Selective 5-hT1B antagonist 10 mg
50 mg
180
720
1253 (S)-WaY 100135 Potent, selective 5-hT1a antagonist 10 mg
50 mg
160
600
4380 WaY 100635 Potent, 5-hT1a silent antagonist; also D4 agonist 10 mg
50 mg
165
635
5-HT2 Receptors
Agonists 1059 BW 723C86 5-hT2B agonist 10 mg
50 mg
145
545
5171 NBOh-2C-CN high affinity, selective 5-hT2a agonist 10 mg
50 mg
210
820
1854 Ro 60-0175 Potent, selective 5-hT2C agonist 10 mg
50 mg
145
560
2592 TCB-2 Potent, high affinity 5-hT2a agonist 10 mg
50 mg
195
760
Antagonists 4173 MDL 100907 Potent and selective 5-hT2a antagonist 10 mg
50 mg
240
935
1644 Mesulergine 5-hT2a and 5-hT2C antagonist; also dopamine receptor partial agonist
10 mg
50 mg
180
705
1955 Ritanserin Potent 5-hT2 antagonist 10 mg
50 mg
80
240
2993 RS 127445 Selective, high affinity 5-hT2B antagonist 10 mg
50 mg
180
720
1661 SB 206553 Potent, selective 5-hT2C/5-hT2B antagonist; orally active 10 mg
50 mg
200
795
1374 SB 215505 5-hT2B/2C antagonist 10 mg
50 mg
180
720
2901 SB 242084 Selective 5-hT2C antagonist; brain penetrant 10 mg
50 mg
195
760
5-HT3 Receptors
Agonists 0558 2-Methyl-5-hydroxytryptamine 5-hT3 agonist; also potent 5-hT6 ligand 10 mg
50 mg
100
355
Antagonists 1795 Zacopride highly potent 5-hT3 receptor antagonist; also 5-hT4 agonist 10 mg
50 mg
145
530
5-HT4 Receptors
Agonists 4374 BIMU 8 Potent 5-hT4 receptor full agonist 10 mg
50 mg
180
705
Antagonists 1322 GR 113808 Potent, selective 5-hT4 antagonist 10 mg
50 mg
175
665
1658 GR 125487 Potent, selective 5-hT4 antagonist; active in vivo 10 mg
50 mg
180
720
Category Cat. No. Product Name Description Unit Size Euro
GPCR ReSeaRCh
tocris.com | 19
Class a: Rhodopsin-like – continued
5-ht5 Receptors
Antagonists 3188 SB 699551 Selective 5-ht5a antagonist 10 mg
50 mg
195
760
5-HT6 Receptors
Agonists 4337 ST 1936 Selective, high affinity 5-hT6 agonist 10 mg
50 mg
175
665
3904 WaY 208466 Selective 5-hT6 agonist 10 mg 190
Antagonists 1961 SB 258585 Potent, selective 5-hT6 antagonist 10 mg
50 mg
165
635
3189 SB 399885 Potent and selective 5-hT6 antagonist 10 mg
50 mg
195
760
5-HT7 Receptors
Agonists 1968 aS 19 Potent 5-hT7 agonist 10 mg
50 mg
180
720
Antagonists 1612 SB 269970 Potent and selective 5-hT7 antagonist; brain penetrant 10 mg
50 mg
195
760
5-HT Receptors (Non-selective)
Agonists 3547 Serotonin endogenous 5-hT receptor agonist 50 mg 80
Antagonists 0996 Cyproheptadine Non-selective 5-hT2 antagonist 50 mg 100
1064 Methysergide 5-hT1/5-hT2 antagonist 10 mg
50 mg
195
760
Class A18 Adenosine A1 Receptors
Agonists 1705 2-Chloro-N6-cyclopentyladenosine Potent, selective a1 agonist 10 mg
50 mg
145
530
3576 (±)-5ʹ-Chloro-5ʹ-deoxy-eNBa highly selective a1 agonist 10 mg
50 mg
195
760
5122 Dansyl-NeCa Potent and selective fluorescent a1 agonist 1 mg 200
Antagonists 0439 DPCPX a1 selective antagonist 100 mg 175
Adenosine A2A Receptors
Agonists 1063 CGS 21680 a2a agonist 10 mg
50 mg
255
1015
4334 PSB 0777 Potent adenosine a2a agonist 10 mg
50 mg
210
820
Antagonists 5147 Istradefylline Potent and selective adenosine a2a antagonist 10 mg
50 mg
160
600
2463 SCh 442416 Very selective, high affinity a2a antagonist 1 mg
10 mg
50 mg
100
195
760
2270 SCh 58261 Potent, highly selective a2a antagonist 10 mg
50 mg
180
720
1036 ZM 241385 Potent, highly selective a2a antagonist 10 mg
50 mg
160
600
Adenosine A2B Receptors
Agonists 4472 BaY 60-6583 Potent a2B agonist; cardioprotective 10 mg
50 mg
180
705
Antagonists 2752 MRS 1754 Selective a2B antagonist 10 mg
50 mg
195
760
2009 PSB 1115 Selective human a2B antagonist; water-soluble 10 mg
50 mg
145
560
3198 PSB 603 highly selective a2B antagonist 10 mg
50 mg
180
695
Category Cat. No. Product Name Description Unit Size Euro
Tocris Product Listing Series
20 |
Adenosine A2A Receptor in Complex with ZM 241385Crystal Structure of the Adenosine A2A Receptor in Complex with the A2A Antagonist ZM 241385
Image adapted from the RSCB PDB (www.rcsb.org) of PDB ID: 3eML Jaakola et al (2008) Science 322 1211. PMID 18832607.
• ZM241385bindsintheA2AbindingpocketlocatedclosetohelicesVIandVII,andinteractswiththeTRP2466.48residue
• ZM241385isapotentandselectiveA2AreceptorantagonistthatexhibitsselectivityforA2AoverA1,A2BandA3receptors
• Thecompoundisactivein vivo
Cat. No. 1036
CXCR4 – IT1t
NN
S
SN
NH
B2-Adrenergic – ICI 118,551
NHHO
O
A2A – ZM 241385
OH
NH
N
N N
N
NO
NH2
D3 – Eticlopride
H1 – Doxepin
O
N
CRF1R – CP-376395
N
O NH
3212
4596 0508
0821
1036MGLUR1 – LY 341495
O
CO2HH2N
OHO
1209
1847
N NH
O HO
OCl
extracellularMembraneIntracellular
Adenosine A3 Receptors
Agonists 1104 2-Cl-IB-MeCa highly selective a3 agonist 10 mg
50 mg
325
1305
1579 heMaDO high affinity and selective a3 agonist 10 mg
50 mg
195
760
1066 IB-MeCa a3 selective agonist 5 mg
25 mg
195
760
5428 MRS 5698 high affinity and selective a3 agonist 1 mg 320
Adenosine Receptors (Non-selective)
Agonists 3624 adenosine endogenous adenosine receptor agonist 50 mg 65
1691 NeCa high affinity adenosine receptor agonist 10 mg
50 mg
70
195
Antagonists 3200 XaC adenosine receptor antagonist 10 mg
50 mg
140
505
Acetylcholine Muscarinic Receptors
Agonists 1067 Oxotremorine M Muscarinic receptor agonist 100 mg 125
3569 Xanomeline Functionally selective M1 agonist 10 mg
50 mg
165
635
Antagonists 1105 aF-DX 116 Selective M2 antagonist 10 mg
50 mg
155
590
1425 (S)-(+)-Dimethindene M2-selective antagonist 10 mg
50 mg
160
600
2507 J 104129 Potent, selective M3 antagonist 10 mg 180
1671 PD 102807 Selective M4 antagonist 10 mg
50 mg
195
760
3727 VU 0255035 highly selective M1 antagonist 10 mg
50 mg
175
665
1414 Scopolamine Non-selective muscarinic antagonist 1 g 80
Modulators 3634 VU 0238429 Selective positive allosteric modulator of M5 receptors 10 mg
50 mg
145
560
3383 VU 152100 Positive allosteric modulator of M4 receptors 10 mg
50 mg
165
635
Category Cat. No. Product Name Description Unit Size Euro
GPCR ReSeaRCh
tocris.com | 21
DREADD LigandsDesigner receptors exclusively activated by designer drugs (DREADDs) are genetically modified GPCRs that are activated by physiologically inert ligands. DREADDs enable the precise experimental manipulation of neuronal signaling, and have multiple non-invasive in vivo applications.
Three new DREADD ligands have recently been added to the Tocris range:
Cat. No. Product name Description
4936 Clozapine N-oxide activator of muscarinic DReaDDs
5548 DREADD agonist 21 NEW Potent muscarinic hM3Dq DReaDD agonist
5549 Perlapine NEW Potent and selective hM3Dq DReaDD agonist
5611 Salvinorin B NEW activates the κ-opioid DReaDD (KORD)
For more information please visit www.tocris.com/DREADDs
Other GPCRs GPBA receptors (TGR5)
Agonists 4478 GPBaR-a GPBa receptor agonist 10 mg
50 mg
210
820
5129 TC-G 1005 Potent and selective GPBa receptor agonist 10 mg
50 mg
195
775
Neuropeptide FF/AF (NPFF) Receptors
Agonists 3137 Neuropeptide FF endogenous NPFF1 and NPFF2 agonist 1 mg 140
5677 RFRP-1 (human) Potent NPFF receptor agonist 1 mg 160
Antagonists 2707 BIBP 3226 Mixed NPFF and NPY Y1 receptor antagonist 1 mg
10 mg
140
270
Orphan GPCRs
Agonists 4177 aS 1269574 GPR119 receptor agonist 10 mg
50 mg
175
665
5666 JNJ 63533054 Potent and selective GPR139 agonist 10 mg
50 mg
145
560
1484 Oleylethanolamide endogenous GPR119 agonist; also GPR55 agonist 10 mg
50 mg
100
345
4074 PF9 Potent GPR17 agonist 1 mg 245
5151 Prosaptide TX14(a) Potent GPR37 and GPR37L1 agonist 1 mg 160
5355 TC-G 1008 Potent and selective GPR39 agonist 10 mg
50 mg
190
740
4255 TC-O 9311 Potent and selective GPR139 agonist 10 mg
50 mg
175
665
Antagonists 5203 NIBR 189 Potent and selective eBI2 (GPR183) receptor antagonist 10 mg
50 mg
165
635
Sensory Neuron-specific Receptor
Agonists 1763 BaM (8-22) Selective agonist for the sensory-neuron specific receptor (SNSR)
1 mg 310
Category Cat. No. Product Name Description Unit Size Euro
Tocris Product Listing Series
22 |
Potent and Selective CGRP Receptor Antagonist
BIBN 4096 Cat. No. 4561
BIBN4096isapotentandselectiveCGRPreceptorantagonist(IC50valuesare0.03and6.4nMforhumanandratCGRPreceptors,respectively).ThecompounddisplayshighaffinityforhumanCGRPreceptors(Ki=14.4pM),andnosignificantaffinityfor75otherreceptors.
JNJ 27141491 (Cat. No. 5176)
N
F
F NHS
OOMe
O N
ML 00253764 (4854)
Br
OMe
F
NHN
TC-G 1008 (5355)
BIBN 4096 (4561)
N
N
N
NH
NH
Cl
NH
SOO
NHN
N
HNO
O
HN
N N NO O
NH2
Br
Br
HO
Purmorphamine (4551)
N
N N
N
NH
O
N
O
CMPD101 (5642)
N
N N
NNH
O
HN
F3C
MA 2029 (4934)
F
N
O
NH
ONHO
HN
OH
Class B: Secretin-likeThe Secretin-like receptor class consists of receptors for neuropeptides and peptide hormones, including glucagon, secretin and calcitonin receptors. The receptors are key drug targets for the study of many human diseases including, diabetes, neurodegeneration, cardiovascular disease, psychiatric disorders and cancer.
Calcitonin and Related Receptors
Agonists 3012 α-CGRP (human) CGRP receptor agonist 1 mg 385
1161 CGRP (rat) CGRP receptor agonist; potent vasodilator 100 µg 140
5031 Pramlintide Synthetic version of amylin (Cat. No. 3418) 500 µg 215
Antagonists 3419 aC 187 Potent and selective amylin receptor antagonist 500 µg 285
4561 BIBN 4096 Potent and selective CGRP receptor antagonist 10 mg 275
1169 CGRP 8-37 (rat) CGRP1 receptor antagonist 500 µg 285
Corticotropin-releasing factor (CRF) Receptors
Agonists 1151 CRF (human, rat) Stimulates aCTh release 200 µg 160
Antagonists 2778 antalarmin CRF1 antagonist 10 mg
50 mg
195
760
2071 antisauvagine-30 Potent, selective and competitive CRF2 antagonist 1 mg 370
2391 astressin 2B Selective CRF2 antagonist 500 µg 370
2779 CP 154526 Selective, non-peptide CRF1 antagonist 10 mg
50 mg
195
760
3212 CP 376395 Potent and selective CRF1 antagonist 10 mg
50 mg
180
720
2070 K 41498 highly selective and potent CRF2 antagonist 1 mg 370
3100 NBI 35965 Potent and selective CRF1 antagonist 10 mg
50 mg
195
780
Gastric Inhibitory Polypeptide (GIP) Receptor
Agonists 2257 GIP (1-39) highly potent insulinotropic peptide 1 mg 325
2084 GIP (human) Potent insulinotropic gut hormone 1 mg 370
Glucagon Receptor
Antagonists 2216 des-his1-[Glu9]-Glucagon (1-29) Glucagon receptor antagonist 1 mg 275
2311 L-168,049 Potent, human glucagon receptor antagonist; orally active 10 mg
50 mg
160
600
Other 2094 Oxyntomodulin endogenous gut peptide; modulates feeding and metabolism 1 mg 305
Category Cat. No. Product Name Description Unit Size Euro
GPCR ReSeaRCh
tocris.com | 23
CRF1 Receptor in Complex with CP 376395Crystal Structure of the CRF1 Receptor in Complex with the CRF1 Antagonist CP 376395
Image adapted from the RSCB PDB (www.rcsb.org) of PDB ID: 4K5Y hollenstein et al (2013) Nature 499 438. PMID 23863939.
• CP376395bindstoahydrophobicpocket,definedbyresiduesofTM3,TM5andTM6,locatedinthecytoplasmicdomainofthereceptor
• CP376395isanon-peptidehighaffinityandselectiveCRF1antagonist(Kivaluesare12and>10,000nMforCRF1andCRF2receptors,respectively)
• ThecompoundattenuatesCRF-inducedHPAaxisactivationin vivo
Cat. No. 3212
CXCR4 – IT1t
NN
S
SN
NH
B2-Adrenergic – ICI 118,551
NHHO
O
A2A – ZM 241385
OH
NH
N
N N
N
NO
NH2
D3 – Eticlopride
H1 – Doxepin
O
N
CRF1R – CP-376395
N
O NH
3212
4596 0508
0821
1036MGLUR1 – LY 341495
O
CO2HH2N
OHO
1209
1847
N NH
O HO
OCl
extracellularMembraneIntracellular
Glucagon-like Peptide Receptors
Agonists 1933 exendin-4 Potent GLP-1 receptor agonist 1 mg 325
5374 GLP-1 (7-37) endogenous bioactive GLP-1 receptor ligand 1 mg 370
2258 GLP-2 (human) endogenous hormone; displays intestinotrophic activity 1 mg 255
2259 GLP-2 (rat) endogenous hormone; displays intestinotrophic activity 1 mg 255
2082 Glucagon-like peptide 1 (7-36) (human, rat)
Potent insulinotropic peptide 1 mg 370
Antagonists 2081 exendin-3 (9-39) Potent GLP-1 receptor antagonist 1 mg 370
3266 GLP-1 (9-36) Metabolite of GLP-1-(7-36) (Cat. No. 2082) 1 mg 285
Modulators 4778 BeTP Positive allosteric modulator of GLP-1 receptors 10 mg
50 mg
175
680
PACAP Receptors
Agonists 1183 PaCaP 1-27 Potent stimulator of adenylyl cyclase 100 µg 145
1186 PaCaP 1-38 Potent stimulator of adenylyl cyclase 100 µg 180
Antagonists 3236 PaCaP 6-38 Potent PaC1 receptor antagonist 100 µg 145
Parathyroid Hormone (PTH) Receptors
Agonists 5487 DPC aJ1951 Potent PTh receptor agonist 1 mg 180
3011 Parathyroid hormone (1-34) (human)
PTh receptor agonist 1 mg 290
Secretin Receptor
Agonists 1918 Secretin (human) Gastrointestinal peptide 1 mg 200
1919 Secretin (rat) Gastrointestinal peptide 1 mg 200
VIP Receptors
Agonists 2711 Bay 55-9837 Potent and selective VPaC2 agonist 1 mg 310
1911 VIP (human, rat, mouse, rabbit, canine, porcine)
endogenous VIP receptor agonist 1 mg 175
Antagonists 3054 [D-p-Cl-Phe6,Leu17]-VIP Selective VIP receptor antagonist 1 mg 255
1905 VIP (6-28) (human, rat, porcine, bovine)
VIP receptor antagonist 1 mg 245
Category Cat. No. Product Name Description Unit Size Euro
Tocris Product Listing Series
24 |
Class C: GlutamateThe Glutamate receptor class of GPCRs consists of receptors that have amino acids, ions and sugars as their endogenous ligands, including glutamate, GABA and calcium. Class C receptors are highly susceptible to modulation by ligands that bind to allosteric binding sites, particularly metabotropic glutamate receptors.
Calcium-sensing Receptor
Agonists 4749 Strontium chloride Calcium sensing receptor (CaSR) agonist 50 mg 55
Antagonists 3626 NPS 2143 Selective antagonist of the calcium-sensing receptor; orally active calcilytic agent
10 mg
50 mg
180
720
Modulators 4387 Calhex 231 Negative allosteric modulator of the calcium-sensing receptor
10 mg
50 mg
215
865
3815 R 568 Positive allosteric modulator of the human calcium-sensing receptor
10 mg
50 mg
155
590
GABAB Receptor
Agonists 0796 (R)-Baclofen Selective GaBaB agonist; active enantiomer of (RS)-Baclofen (Cat. No. 0417)
10 mg
50 mg
100
325
3400 RuBi-GaBa Caged GaBa; excitable by visible wavelength 10 mg 195
Antagonists 1245 CGP 35348 Brain penetrant, selective GaBaB antagonist 10 mg
50 mg
180
720
1246 CGP 52432 Potent, selective GaBaB antagonist 10 mg
50 mg
195
760
1088 CGP 54626 Potent, selective GaBaB antagonist 10 mg
50 mg
195
760
1248 CGP 55845 Potent, selective GaBaB antagonist 10 mg
50 mg
195
775
0984 SCh 50911 Selective, competitive, orally active GaBaB antagonist 10 mg
50 mg
210
820
Modulators 1513 CGP 7930 Positive modulator at GaBaB receptors 10 mg
50 mg
145
520
Glutamate (Metabotropic) Group I Receptors
Agonists 0187 (±)-trans-aCPD Group I/group II mGlu agonist 10 mg
50 mg
180
705
1049 ChPG mGlu5 selective agonist 10 mg
50 mg
125
430
3695 ChPG Sodium salt Selective mGlu5 agonist; sodium salt of ChPG (Cat. No. 1049)
10 mg
50 mg
130
465
0342 (RS)-3,5-DhPG Selective group I mGlu agonist 1 mg
10 mg
50 mg
80
145
545
0805 (S)-3,5-DhPG Selective group I mGlu agonist; active enantiomer of 3,5-DhPG (Cat. No. 0342)
5 mg
10 mg
145
255
0188 L-Quisqualic acid Group I mGlu agonist; also aMPa receptor agonist 1 mg
10 mg
50 mg
95
180
720
Antagonists 5614 aZD 2066 mGlu5 antagonist; orally bioavailable and brain penetrant 10 mg 180
2501 Bay 36-7620 Non-competitive mGlu1 antagonist with inverse agonist activity
10 mg 215
0323 (S)-4-Carboxyphenylglycine Competitive group I mGlu antagonist/weak group II agonist 10 mg
50 mg
255
1015
1028 CPCCOet Selective non-competitive mGlu1 receptor antagonist 10 mg
50 mg
145
560
2333 JNJ 16259685 highly potent, mGlu1-selective non-competitive antagonist
10 mg
50 mg
215
865
1237 LY 367385 Selective mGlu1a antagonist 10 mg
50 mg
175
665
Category Cat. No. Product Name Description Unit Size Euro
GPCR ReSeaRCh
tocris.com | 25
Glutamate (Metabotropic) Receptors
NMe
NN
HN
O
CN
F
O
HN
O
N
N
S
N
N
Cl O
O
Cl
NH
O N
Cl
MPEP (1212)mGlu5 antagonist and positive allosteric
modulator at mGlu4
CDPPB (3235)Positive allosteric modulator at mGlu5
VU 0409106 (5322)Potent and selective negative allosteric
modulator at mGlu5
VU 0483605 (5377)Positive allosteric modulator at mGlu1
LY 487379 (3283)Positive allosteric modulator selective for mGlu2
O
OMe N
NSO O
F3C
Glutamate (Metabotropic) Receptor Allosteric Modulators
3696 (RS)-MCPG disodium salt Sodium salt of (RS)-MCPG (Cat. No. 0336) 10 mg
50 mg
145
560
1212 MPeP mGlu5 antagonist and positive allosteric modulator at mGlu4
10 mg
50 mg
145
520
2921 MTeP Potent, selective mGlu5 antagonist 10 mg
50 mg
160
600
Modulators 3235 CDPPB Positive allosteric modulator at mGlu5 10 mg
50 mg
165
635
5275 LSN 2463359 Potent and selective positive allosteric modulator at mGlu5
10 mg
50 mg
165
635
5322 VU 0409106 Potent and selective negative allosteric modulator at mGlu5
10 mg
50 mg
145
560
5377 VU 0483605 Positive allosteric modulator at mGlu1 10 mg
50 mg
145
560
Glutamate (Metabotropic) Group II Receptors
Agonists 0975 DCG IV Very potent, selective group II mGlu agonist; also NMDa agonist
1 mg
10 mg
50 mg
195
405
1660
3246 LY 354740 Potent and highly selective group II mGlu agonist 10 mg
50 mg
195
760
2453 LY 379268 highly selective group II mGlu agonist 10 mg
50 mg
325
1325
5064 LY 379268 disodium salt Selective group II mGlu receptor agonist; sodium salt of LY 379268 (Cat. No. 2453)
10 mg
50 mg
340
1360
Antagonists 1209 LY 341495 highly potent, selective group II antagonist 1 mg
10 mg
50 mg
100
225
965
4062 LY 341495 disodium salt Disodium salt of LY 341495 (Cat. No. 1209) 1 mg
10 mg
50 mg
125
240
935
0337 (S)-MCPG Non-selective mGlu antagonist; active isomer of (RS)-MCPG (Cat. No. 0336)
10 mg
50 mg
245
980
Modulators 3283 LY 487379 Positive allosteric modulator selective for mGlu2 10 mg
50 mg
160
600
Category Cat. No. Product Name Description Unit Size Euro
Tocris Product Listing Series
26 |
mGlu1 Receptor in Complex with LY 341495Crystal Structure of the mGlu1 Receptor in Complex with the Group II mGlu Receptor Antagonist LY 341495
Image adapted from the RSCB PDB (www.rcsb.org) of PDB ID: 3KS9 Dobrovetsky et al (2009) Data yet to be published.
• DataregardingthebindingofLY341495tomGlu1haveyettobepublished
• LY341495isapotentandselectivegroupIImGlureceptorantagonist(IC50valuesare1.3and2.3nMformGlu3andmGlu2receptors,respectively)thatexhibitsselectivityovergroupIandIIImGlureceptors
• Thecompoundisbrainpenetrantandactivein vivo
Cat. No. 1209
CXCR4 – IT1t
NN
S
SN
NH
B2-Adrenergic – ICI 118,551
NHHO
O
A2A – ZM 241385
OH
NH
N
N N
N
NO
NH2
D3 – Eticlopride
H1 – Doxepin
O
N
CRF1R – CP-376395
N
O NH
3212
4596 0508
0821
1036MGLUR1 – LY 341495
O
CO2HH2N
OHO
1209
1847
N NH
O HO
OCl
Glutamate (Metabotropic) Group III Receptors
Agonists 2385 aMN 082 The first selective mGlu7 agonist 10 mg
50 mg
125
445
0103 L-aP4 Selective group III mGlu agonist 1 mg
10 mg
50 mg
95
180
705
Antagonists 0972 CPPG Very potent group III mGlu antagonist 10 mg
50 mg
165
635
2963 MMPIP Potent, allosteric mGlu7-selective antagonist 1 mg
10 mg
50 mg
85
165
635
Category Cat. No. Product Name Description Unit Size Euro
GPCR ReSeaRCh
tocris.com | 27
GPCR allosteryGPCR allostery refers to the binding of ligands at sites on the receptor distinct from the orthosteric binding site, termed allosteric binding sites. Allosteric ligands can have intrinsic agonist/inverse agonist activity of their own, potentiate/decrease the effects of orthosteric ligands, or be neutral ligands with no intrinsic/modulatory activity.
Allosteric Modulation:
allosteric modulators are ligands that bind to receptor allosteric binding sites and influence the binding affinity and/or the signaling efficacy of the orthosteric ligand.
Those that potentiate the action of an orthosteric ligand are termed positive allosteric modulators (PaMs), whereas those that decrease the action are termed negative allosteric modulators (NaMs).
Unlike some allosteric ligands that have intrinsic agonist activity, allosteric modulators only have an effect in the presence of an orthosteric ligand (a ligand that binds to the binding site of the receptors endogenous ligand). They therefore have the advantage of being able to selectively influence physiological processes in tissues where the endogenous ligand is present.
allosteric modulators have been developed for Class a, B and C GPCRs. They are especially useful for Class B GPCRs, which have orthosteric binding sites that are difficult to target pharmacologically.
Key Characteristics of GPCR Allostery:
Enhanced Selectivity:allosteric binding sites have greater sequence divergence than the often conserved orthosteric site between receptor subtypes. Therefore allosteric ligands have the potential to offer greater subtype selectivity for receptors, such as the acetylcholine musarinic receptor.
The Saturation Effect:The effect of an allosteric ligand reaches a saturation point over a certain concentration, whereby no further pharmacological effects are observed. This enables greater fine-tuning of physiological responses, and lowers the risk of target-based overdose.
Probe Dependence:The effect of an allosteric modulator can be dependent on the orthosteric ligand. For example the adenosine a1 receptor allosteric modulator PD 81723 (Cat. No. 1363) enhances the affinity of the agonist [3h]Cha, but not the antagonist [3h]CPX, for the a1 receptor.
Biased Signaling:Biased agonism/modulation refers to the ability of allosteric (and orthosteric) ligands to preferentialy induce certain intracellular signaling pathways at the exclusion of others. allosteric modulators can also impose bias signaling on certain orthosteric agonists. See pg 30 for more information.
For references and further reading please see pg 31
Allosteric Modulation SchematicSchematic representing orthosteric and allosteric GPCR signaling. Positive allosteric modulators (PaMs) potentiate the binding affinity (dark green pointed arrow) and/or signaling efficacy (light red pointed arrow) of the orthosteric ligand, whereas negative allosteric modulators (NaMs) decrease the binding affinity (dark green flat arrow) and/or the signaling efficacy (light red flat arrow) of the orthosteric ligand. Neutral allosteric ligands have no intrinsic activity and have no effect on orthosteric signaling, although they are able to block the binding of other allosteric ligands to the allosteric binding site that they occupy. allosteric modulators exert their effects on orthosteric ligand-induced signaling by stabilizing the receptor in a conformation that is either favorable (PaMs) or unfavorable (NaMs) towards the ligands binding affinity and/or signaling efficacy. Figure adapted from Wooten et al (2013) Nat.Rev.Drug Discov. 12 630.
Orthosteric Signaling Positive Allosteric Modulation Negative Allosteric Modulation Neutral Allosteric Ligand
Signaling Potentiated signaling Reduced signaling Unaltered signaling
Neutral allosteric ligand
Orthosteric agonist
G protein
PAM NAM
Tocris Product Listing Series
28 |
Class F: FrizzledThe Frizzled receptor class of GPCRs consists of frizzled (FZD) receptors, FZD1-8 and the smoothened receptor (SMOH), and taste receptors. FZD1-8 are activated by Wnt proteins, whereas SMOH is activated by Hedgehog (Hh) signaling. The SMOH receptor is unique in that it does not directly interact with its endogenous ligand.
Smoothened Receptor Agonist
Purmorphamine Cat. No. 4551
Purmorphamineisasmoothenedreceptoragonistthatinducesosteogenesisinmousemesenchymalprogenitorcells.Thecompoundalsotransdifferentiatespre-adipocytesandmyoblastsintoosteoblastsincombinationwithBMP-4.
JNJ 27141491 (Cat. No. 5176)
N
F
F NHS
OOMe
O N
ML 00253764 (4854)
Br
OMe
F
NHN
TC-G 1008 (5355)
BIBN 4096 (4561)
N
N
N
NH
NH
Cl
NH
SOO
NHN
N
HNO
O
HN
N N NO O
NH2
Br
Br
HO
Purmorphamine (4551)
N
N N
N
NH
O
N
O
CMPD101 (5642)
N
N N
NNH
O
HN
F3C
MA 2029 (4934)
F
N
O
NH
ONHO
HN
OH
Licensing at TocrisTocris Bioscience has a long tradition of working with scientists to bring new discoveries out of the laboratory and into the commercial arena. We work in partnership with many scientists within both Universities and pharmaceutical companies to bring life science tools to the global research community.
The Tocris policy has always been to never knowingly infringe third party intellectual property. It is our intention to remain a responsible and ethical supplier, and work with the scientific community.
Our ExpertiseOur licensing department has significant experience of drafting contracts and has successfully executed licenses with a multitude of licensors, including:
• Large pharmaceutical companies• Start-up/spin-out companies • University technology transfer offices• Individual researchers
Contact UsTo discuss licensing opportunities, please contact our licensing team at [email protected]
Smoothened Receptor
Agonists 4551 Purmorphamine Smo receptor agonist 10 mg
50 mg
180
720
4366 SaG Potent Smoothened receptor agonist; activates the hedgehog signaling pathway
1 mg 155
Antagonists 1623 Cyclopamine Inhibitor of hedgehog (hh) signaling; antagonizes smoothened activity
1 mg 180
5554 IhR 1 Potent Smo antagonist 10 mg
50 mg
125
470
1974 SaNT-1 Inhibitor of hedgehog (hh) signaling; antagonizes smoothened activity
10 mg
50 mg
175
665
Category Cat. No. Product Name Description Unit Size Euro
GPCR ReSeaRCh
tocris.com | 29
GPCR SignalingGPCRs mediate signal transduction from the cytosol to the cell interior. Agonist binding to GPCRs results in the coupling of heterotrimeric G proteins, which are subsequently released by GDP/GTP exchange. The G protein subunits activate effector proteins, such as cyclases and phospholipases to induce intracellular signaling cascades.
Adenylyl Cyclase
Activators 1099 Forskolin adenylyl cyclase activator 10 mg
50 mg
145
560
1603 NKh 477 Water-soluble adenylyl cyclase activator 10 mg
50 mg
210
820
Inhibitors 1435 SQ 22536 adenylyl cyclase inhibitor 10 mg
50 mg
145
545
cAMP
Other 5255 6-Bnz-caMP sodium salt Cell permeable caMP analog 1 mg 140
1140 8-Bromo-caMP, sodium salt Cell-permeable caMP analog 10 mg
50 mg
80
240
1337 caMPS-Rp caMP antagonist 1 mg 145
1333 caMPS-Sp Cell-permeable caMP analog 1 mg 145
1141 Dibutyryl-caMP, sodium salt Cell-permeable caMP analog 10 mg
50 mg
100
325
G Protein (Heterotrimeric)
Inhibitors 4567 CCG 50014 Potent and selective inhibitor of regulator of G-protein signaling 4 (RGS4) protein
10 mg
50 mg
175
665
4773 eSI 09 ePaC inhibitor 10 mg
50 mg
165
635
3090 Gallein Inhibitor of βγ signaling 50 mg 85
Other 3097 Pertussis Toxin Catalyzes aDP-ribosylation of Gi, Go and Gt 50 µg 335
GRK
Inhibitors 5642 CMPD101 Potent and selective GRK2/3 inhibitor 10 mg 140
3594 GRK2i GRK2 inhibitory polypeptide; Gβγ antagonist 1 mg 215
IP3 Receptor
Antagonists 1224 2-aPB IP3 receptor antagonist; also TRP channel modulator 10 mg
50 mg
80
240
Other 1280 (-)-Xestospongin C Reported inhibitor of IP3-dependent Ca2+ release 10 µg 195
Phospholipases
Inhibitors 1437 D609 Selective PC-PLC inhibitor 10 mg
50 mg
140
450
3022 edelfosine Selective PI-PLC inhibitor; also PaF receptor agonist 10 mg 125
3600 FIPI Phospholipase D inhibitor 10 mg
50 mg
215
865
1268 U 73122 Phospholipase C inhibitor 10 mg
50 mg
145
530
4133 U 73343 analog of U 73122 (Cat. No. 1268) 10 mg
50 mg
140
520
3575 VU 0155069 Potent and selective PLD1 inhibitor 10 mg
50 mg
195
775
4171 VU 0364739 Potent and selective PLD2 inhibitor 10 mg
50 mg
225
900
2522 YM 26734 Secretory phospholipase a2 (sPLa2) inhibitor 10 mg 180
Category Cat. No. Product Name Description Unit Size Euro
Tocris Product Listing Series
30 |
Activation
Inhibition
Movement
Blocked effect
Gαs
GαiGαq Gα
AC PLC Raf ASK1
MEK1 MEK4 PI 3-K RhoA c-Src
ERK JNK Akt ROCK
cAMP ATP
PKA EPAC
IP3 DAG
Ca2+ PKC
β-arrestin
GRK5/6
GRK5/6
G Protein-dependent Signaling β-Arrestin-dependent Signaling
β-arrestin PP
Bias SignalingBiased agonism or functional selectivity is the phenomenon whereby ligands can selectively activate certain signaling pathways, while others remain inactive. Biased ligands can stabilize their GPCR in different active conformations, resulting in bias towards certain pathways such as G protein- or β-arrestin-dependent signaling.
Allosteric Modulation and Bias Signaling:as well as many orthosteric ligands being identified as bias agonists, allosteric ligands have also been shown to exhibit signal bias (for an overview of allosteric modulation see pg 27). Certain allosteric modulators have the ability to direct orthosteric agonist signaling towards specific signaling pathways. For example ORG 27569 (Cat. No. 2957) acts as a negative allosteric modulator (NaM) of orthosteric agonist-mediated CB1 Gαs signaling and a positive allosteric modulator (PaM) on β-arrestin signaling, while Gadolinium (Cat. No. 4741) is a PaM of agonist-mediated mGlu1α Gαq signaling and a NaM on Gαs signaling. The discovery of allosteric ligands that can direct orthosteric ligand signal bias offers the potential for the augmentation of desirable physiological signaling pathways to produce more effective therapeutic drugs.
Biased Signaling Schematic
Schematic representing biased signaling towards G protein- and β-arrestin signaling. GPCR signaling classically results in the downstream activation of G proteins, which stimulate intracellular effectors such as aC and PLC. activated GPCRs are phosphorylated by GRKs, recruiting β-arrestin to the receptor and stimulating further signaling pathways such as MaPK, PI 3-K, Rhoa and c-Src signaling. Ligands have recently been developed that can selectively activate G protein- or β-arrestin-dependent signaling, while having no significant effect on the other pathway. Certain ligands can also stimulate specific Gα proteins over others. This phenomenon was termed biased agonism. These biased ligands can induce GPCRs to adopt certain active conformations that preferentially activate different intracellular signaling pathways.abbreviations: aC, adenylyl cyclase; akt, protein kinase B; caMP, cyclic adenosine monophosphate; aSK1, apoptosis signal-regulating kinase 1; aTP, adenosine triphosphate; DaG, diacylglycerol; ePaC, exchange factor directly activated by caMP 1; eRK, extracellular signal–regulated kinase; GRK, G protein-coupled receptor kinase; IP3, inositol trisphosphate; JNK, c-Jun N-terminal kinase; MeK, mitogen-activated protein kinase kinase; PI 3-K, phosphatidylinositol-4,5-bisphosphate 3-kinase; PKa, protein kinase a; PKC, protein kinase C; PLC, phospholipase C; Rhoa, Ras homolog gene family, member a; ROCK, Rho-associated protein kinase.
GPCR ReSeaRCh
tocris.com | 31
GPCRCrystalStructures:
Bortolato et al (2014) Structure of Class B GPCRs: new horizons for drug discovery. Br.J.Pharmacol. 171 3132Granier and Kobilka (2012) A new era of GPCR structural and chemical biology. Nat.Chem.Biol. 8 670Stevens et al (2013) The GPCR Network: a large-scale collaboration to determine human GPCR structure and function. Nat.Rev.Drug Discov. 12 25Tautermann (2014) GPCR structures in drug design, emerging opportunities with new structures. Bioorg.Med.Chem.Lett. 24 4073
GPCRAllostery:
Christopoulos (2014) Advances in G protein-coupled receptor allostery: from function to structure. Mol.Pharmacol. 86 463Christopoulos et al (2014) International Union of Basic and Clinical Pharmacology. XC. multisite pharmacology: recommendations for the nomenclature of receptor allosterism and allosteric ligands. Pharmacol.Rev. 66 918Kollias-Baker et al (1994) Allosteric enhancer PD 81,723 acts by novel mechanism to potentiate cardiac actions of adenosine. Circ.Res. 75 961Müller et al (2012) Allosteric modulators of rhodopsin-like G protein-coupled receptors: opportunities in drug development. Pharmacol.Ther. 135 292Wooten et al (2013) Emerging paradigms in GPCR allostery: implications for drug discovery. Nat.Rev.Drug Discov. 12 630
BiasSignaling:
Kenakin and Christopoulos (2013) Signalling bias in new drug discovery: detection, quantification and therapeutic impact. Nat.Rev.Drug Discov. 12 205Khoury et al (2014) Allosteric and biased G protein-coupled receptor signaling regulation: potentials for new therapeutics. Front.Endocrinol. 5 1Rankovic et al (2014) Biased agonism: An emerging paradigm in GPCR drug discovery. Bioorg.Med.Chem.Lett. 26 241Sonoda et al (2014) β-Arrestin-1 mediates glucagon-like peptide-1 signaling to insulin secretion in cultured pancreatic beta cells. Proc.Natl.Acad.Sci.U.S.A. 105 6614
References and Further Reading
Analgesia:
• Morphine (Cat. No. 5158), an opioid receptor agonist, is commonly used clinically to relieve pain
• β-arrestin knock-out mice administered morphine experience enhanced analgesia and fewer side effects, such as respiratory and gastrointestinal dysfunction
• The development of opioid receptor bias agonists that selectively activate G protein signaling may result in improved analgesic drugs without the adverse side effects
Antipsychotics:
• Dopamine D2 receptor antagonists are clinically used as antipsychotics, but are associated with motor side effects such as catalepsy and dyskinesias
BiasSignaling(cont.):
Therapeutic Applications:Biased agonism is of great interest therapeutically as it offers the potential to preferentially activate signaling pathways that induce the desired physiological effect, while having no effect on those that cause adverse side effects. Biased agonists have the potential to revolutionize the drug discovery process, through the generation of safer and more effective drugs.
• β-arrestin biased D2 agonists have been recently developed that exhibit antipsychotic activity in mice without the motor side effects
Cardiovascular Disease:
• angiotensin II receptor type 1 (aT1) antagonists have long been used in the treatment of hypertension, however reduced cardiac output is a side effect
• The β-arrestin biased aT1 antagonist TRV027 has been shown to reduce blood pressure and enhance cardiac performance in rats
• Furthermore β-arrestin biased aT1 agonists have been found to protect against cell death during cardiac injury, which could be applied to the treatment of cardiac ischemia
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