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The University of California, Santa Barbara
Department of Chemistry & Biochemistry
Presents
THE THIRTY-FIFTH ANNUAL
B. R. BAKER LECTURE
Delivered by

Christopher A. Lipinski
Pfizer Global Research
"Overcoming Efficacy Failure: Drug Repurposing Is The Positive Face Of Drug Discovery Poor Clinical Efficacy Prediction"
Thursday, May 7, 2009 at 3:30 p.m.
Chemistry 1179
Chris Lipinski received his Ph.D. in 1968 in physical organic chemistry
from the University of California, Berkeley. He subsequently served as
a NIH Postdoctoral fellow at the California Institute of Technology with
Bob Ireland. At the Pfizer
Global Research and Development Groton Laboratories
from
1970 to 1990, Dr. Lipinski oversaw the development of numerous drug
candidates for the treatment of gastrointestinal and diabetic
diseases. While working at Pfizer, he became very interested in the
design of bioisosteres for improving efficacy as well as in the physical
chemical properties of compounds that ultimately relate to their
adsorption, distribution, metabolism, excretion and toxicity (ADMET).
He subsequently published a landmark paper, "Experimental and
computational approaches to estimate solubility and permeability in drug
discovery and development settings" Advanced Drug Delivery Reviews,
1997, 23, 3-25, which has been cited over sixteen hundred times and
which averages over one hundred and twenty citations per year. In this
publication, Dr. Lipinski has championed a very pragmatic approach to
the problem of oral activity improvement for drug candidates, that has
become known as "The Rule of Five
" based on the
observation that most medication drugs are relatively small and
lipophilic molecules. This publication has significantly influenced
the way that the pharmaceutical industry approaches the development of
orally active drugs. Lipinski's rule states that, in general, an orally
active drug has no more than one violation of the following criteria:
not more than 5 hydrogen bond donors, not more than 10 hydrogen bond
acceptors, a molecular weight of under 500 daltons, and an octanol-water
partition coefficient log P of less than 5. Note that all numbers are
multiples of five, hence the origin of the rule's name. The rule
filters out molecules that are likely to have poor intestinal
permeability or poor aqueous solubility, and hence poor oral absorption.
Today drug discovery programs worldwide use the Rule in their go/no-go
decision-making processes.
Dr. Lipinski is a member of the TB Alliance Scientific Advisory
Committee. He is recipient of an honorary law degree from the
University of Dundee , a winner of
Society for Biomolecular Sciences (SBS) 2006 Achievement Award for
Innovation in HTS
,
winner of the 2005
E. B. Hershberg Award for Important Discoveries in Medicinally Active
Substances
from
the American Chemical Society, 2004 winner of the Medicinal Chemistry
Award from the American
Chemical Society Division of Medicinal Chemistry. Dr. Lipinski has been
an adjunct faculty member at Connecticut College in New London CT since
1984, and has over 210 publications and invited presentations and 17
issued US patents. He is presently a consultant for Melior Discovery,
Inc
Professor
B.R. Baker was a Professor of Chemistry at UCSB from 1966 until
his death in 1971. Baker's graduate work on the structural elucidation
and synthesis of Cannabis constituents marked the beginning
of a prolific career in the chemistry of natural products. He undertook
many diverse projects of medicinal interest including the synthesis
of antihemorrhagic vitamin K analogues, biotin derivatives, compounds
with hormone activity, sulfones with activity against tuberculosis,
and alkaloids. He published two books and more than 370 papers that
included a series of papers on the structure and synthesis of the
antimalarial alkaloid from Hydrangea that filled an entire
issue of the Journal of Organic Chemistry in 1952. He determined
the structure of the first known nucleoside antibiotic, puromycin,
and synthesized it in 1955. This achievement came long before the
discovery of the structure of transfer ribonucleic acid (tRNA).
Puromycin was later shown to mimic the structure of tRNA and became
and an important tool of research in molecular biology. Puromycin
was too toxic for cancer chemotherapy, but it aroused Bill's interest
in this field. Few of the myriad of compounds that he had so meticulously
synthesized showed any antitumor activity in vivo, so he
sought a more rational approach to cancer chemotherapy. Perhaps
his greatest contribution to medicinal chemistry was the concept
of active-site-directed irreversible enzyme inhibition of substrate-identical
enzymes. A monograph summarizing this approach to drug design promptly
became on of the classic works in the field.
Past
lecturers:
| Year |
Presenter |
Institution |
|
Year |
Presenter |
Institution |
| 2008 |
Robert Stroud |
UCSF |
|
|
|
|
| 2007 |
Vern
Schramm |
Yeshiva
Univ. |
|
1990 |
Sir
James W. Black |
Kings
College |
| 2006 |
Paul
J. Reider |
Amgen |
|
1989 |
E.J.
Corey |
Harvard |
| 2005 |
Ronald
Breslow |
Columbia
Univ. |
|
1988 |
Richard
Lerner |
Scripps
Found. |
| 2004 |
T.C.
Bruice |
UCSB |
|
1987 |
Harry
B. Gray |
Cal
Tech |
| 2003 |
Jack
Dixon |
UCSD |
|
1986 |
Alan
R. Fersht |
Imperial
College |
| 2002 |
Gregory
Petsko |
Brandeis
Univ. |
|
1985 |
Stephen
Benkovic |
Penn
State |
| 2001 |
Steven
Benner |
Florida
Univ. |
|
1984 |
Christopher
Walsh |
Harvard
Med. |
| 2000 |
Joanne
Stubbe |
MIT |
|
1983 |
|
|
| 1999 |
Richard
E. Dickerson |
UCLA |
|
1982 |
Daniel
Santi |
UC
San Francisco |
| 1998 |
Harold
A. Sheraga |
Cornell
Univ. |
|
1981 |
Carl
Djerassi |
Stanford
Univ. |
| 1997 |
Daniel
E. Koshland |
Berkeley |
|
1980 |
Linus
Pauling |
|
| 1996 |
David
S. Sigman |
UCLA |
|
1979 |
Bruce
N. Ames |
Berkeley |
| 1995 |
Chi-Huey
Wong |
Scripps
Inst. |
|
1978 |
Jeremy
Knowles |
Harvard
Univ. |
| 1994 |
Richard
Holm |
Harvard
Univ. |
|
1977 |
|
|
| 1993 |
Olke
C. Uhlenbeck |
Colorado
Univ. |
|
1976 |
Nelson
Leonard |
Illinois
Univ. |
| 1992 |
Peter
B. Dervan |
CAL
Tech |
|
1975 |
Joseph
Bertino |
Yale
Univ. |
| 1991 |
Peter
G. Schultz |
Berkeley |
|
1975 |
Paul
Berg |
Stanford
Univ. |
|