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
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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
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)
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.
LeMaistre Clinic Buildingopened in 1996 -- 15,756 sq. m.
Alkek Hospital Buildingopened in 1998 -- 70,212 sq. m.
Mays Clinical Buildingopened in 2004 --113,112 sq. m.
Texas Medical Center
Co-Branded Institutions
Sister Institutions
Breast Awareness and Research Partnerships
MDACC
UT MD Andersons Sister Institution Network
FranceInstitut Gustave Roussy, Villejuif
GermanyGerman Cancer Research Center, Heidelberg
Norway The Norwegian Cancer Consortium
PolandThe Polish Cancer Consortium
Sister Institutions
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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
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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
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
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
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