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Chemistry and Biology of Cancer ----------- Drug Discovery in Academia Waldemar Priebe, Ph.D. Professor of Chemistry and Professor of Medicinal Chemistry Destination Europe POLAND San Francisco December 7, 2012

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Page 1: Chemistry and Biology of Cancer ----------- Drug Discovery in Academia Waldemar Priebe, Ph.D. Professor of Chemistry and Professor of Medicinal Chemistry

Chemistry and Biology of Cancer-----------

Drug Discovery in Academia

Waldemar Priebe, Ph.D.Professor of Chemistry and

Professor of Medicinal Chemistry

Destination Europe

POLAND

San FranciscoDecember 7, 2012

Page 2: Chemistry and Biology of Cancer ----------- Drug Discovery in Academia Waldemar Priebe, Ph.D. Professor of Chemistry and Professor of Medicinal Chemistry

2

Waldemar Priebe

• Professor, Medicinal Chemistry, UT MD Anderson Cancer Center

• Over 25 years research experience in drug discovery and development

• Founder or Founding Scientist of 5 Biotech Co.

• Aronex Pharmaceuticals

• Houston Pharmaceuticals

• Reata Pharmaceuticals

• Moleculin, LLC

• IntertechBio

• Licensed 7 compounds to industry with 4 drugs in clinical studies in humans

• Over 180 research papers and 50 patents

Importance of Entrepreneurial Scientists to the Future of the EU and American Economy

Page 3: Chemistry and Biology of Cancer ----------- Drug Discovery in Academia Waldemar Priebe, Ph.D. Professor of Chemistry and Professor of Medicinal Chemistry

TEXAS:an overview

Population: 23 mln

Labor Force: 11 mln

Unemployment Rate: 4.2 %

2nd Most Populous State

261,797 square miles of land (twice as Germany)

http://www.globus.camcom.it/intranet/Aree-Terri/Internazio/Houston/Perche--Texas.doc_cvt01.jpg
Page 4: Chemistry and Biology of Cancer ----------- Drug Discovery in Academia Waldemar Priebe, Ph.D. Professor of Chemistry and Professor of Medicinal Chemistry

History of The University of Texas MD Anderson Cancer Center

Monroe Dunaway Anderson created a charitable foundation in 1936. After his death, the MD Anderson Foundation provided funding and land to build a cancer hospital to serve the citizens of Texas.

Page 5: Chemistry and Biology of Cancer ----------- Drug Discovery in Academia Waldemar Priebe, Ph.D. Professor of Chemistry and Professor of Medicinal Chemistry

LeMaistre Clinic Buildingopened in 1996 -- 15,756 sq. m.

Page 6: Chemistry and Biology of Cancer ----------- Drug Discovery in Academia Waldemar Priebe, Ph.D. Professor of Chemistry and Professor of Medicinal Chemistry

Alkek Hospital Buildingopened in 1998 -- 70,212 sq. m.

Page 7: Chemistry and Biology of Cancer ----------- Drug Discovery in Academia Waldemar Priebe, Ph.D. Professor of Chemistry and Professor of Medicinal Chemistry

Mays Clinical Buildingopened in 2004 --113,112 sq. m.

Page 8: Chemistry and Biology of Cancer ----------- Drug Discovery in Academia Waldemar Priebe, Ph.D. Professor of Chemistry and Professor of Medicinal Chemistry

Texas Medical Center

Page 9: Chemistry and Biology of Cancer ----------- Drug Discovery in Academia Waldemar Priebe, Ph.D. Professor of Chemistry and Professor of Medicinal Chemistry

Co-Branded Institutions

Sister Institutions

Breast Awareness and Research Partnerships

MDACC

UT MD Andersons Sister Institution Network

Page 10: Chemistry and Biology of Cancer ----------- Drug Discovery in Academia Waldemar Priebe, Ph.D. Professor of Chemistry and Professor of Medicinal Chemistry

FranceInstitut Gustave Roussy, Villejuif

GermanyGerman Cancer Research Center, Heidelberg

Norway The Norwegian Cancer Consortium

PolandThe Polish Cancer Consortium

Sister Institutions

10

Page 11: Chemistry and Biology of Cancer ----------- Drug Discovery in Academia Waldemar Priebe, Ph.D. Professor of Chemistry and Professor of Medicinal Chemistry

Structure of the WP631–AC/GTAC/GT Complex

Kobs = 3 x 1011 M-1

WP631 inhibits (at 60 nM) Sp1-activated transcription initiation in vitro

WP631

1

J. Med. Chem., 40: 261-266, 1997Biochemistry, 36: 5940-5946, 1997Biochemistry, 36: 8663-8670, 1997Biochemistry, 37: 1743-1753, 1998Nucleic Acid Res., 27: 3402-3409, 1999Curr. Med Chem. 8: 1-8, 2001J. Biol. Chem., 276: 34486, 2001Methods in Enzymology, Vol. 340, 529-555, 2001

Waldemar Priebe

Biochem. Pharmacol. 63, 1251-1258, 2002Eur. J. Biochem., 270: 764-770, 2003Biochemistry. 43(23):7584-7592, 2004Eur. J. Biochem., 271, 3556–3566, 2004J. Med. Chem., 48, 8209-8219, 2005

Page 12: Chemistry and Biology of Cancer ----------- Drug Discovery in Academia Waldemar Priebe, Ph.D. Professor of Chemistry and Professor of Medicinal Chemistry

Patient Examples in Phase I Trial of WP744 (RTA744, Berubicin)

Before RTA 744Oct 20, 2006

After 2 Cycles

Patient 119 Achieves Partial Response After 2 Cycles of RTA 744 at a Dose of 7.5 mg/m2/day x 3

52 Year-old female

Diagnosed with AO December 2000

Previous treatments include resection, RT, resection, Tmz, resection

81% reduction in lesion

Page 13: Chemistry and Biology of Cancer ----------- Drug Discovery in Academia Waldemar Priebe, Ph.D. Professor of Chemistry and Professor of Medicinal Chemistry

Before RTA 744Jan 20

After 2 CyclesMar 7

After 6 CyclesJuly 11

After 7 CyclesAug 1

Patient 104 Achieves Complete Response After 7 Cycles of RTA 744 at a Dose 2.4 mg/m2/day x 3

52 year-old male

Recurrent GBM progressed from AA

Previous treatments include resection, RT + Tmz,Tmz + Thalidomide + Accutane + Celebrex (8 cycles)

Complete Response ongoing 3 years later

Evidence of Clinical Activity of Berubicin (RTA744/WP744) in Phase I

Page 14: Chemistry and Biology of Cancer ----------- Drug Discovery in Academia Waldemar Priebe, Ph.D. Professor of Chemistry and Professor of Medicinal Chemistry

F18-FDG PET Baseline Study

F18-FDG PET Scan of “Hot” Tumor Treated with 2-DG

24 Hours Repeat F18-FDG PET Post Treatment with 2-DG


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