Dr. Christopher A. Lipinski

Dr. Lipinski retired from the position of Senior Research Fellow in the Exploratory Medicinal Sciences Department at the Pfizer Global Research and Development Groton Laboratories in June 2002. He received a B.Sc. degree in chemistry from San Francisco State College in 1965 and a Ph.D. in 1968 in physical organic chemistry from the University of California, Berkeley. He joined Pfizer in 1970 following a National Institutes of General Medical Sciences Postdoctoral Fellowship at the California Institute of Technology. At Pfizer, from 1970 to 1990, he supervised medicinal chemistry drug discovery laboratories discovering multiple gastrointestinal and diabetic clinical candidates. In this process he became interested in the design of bioisosteres and in drug physical chemical properties and quantitative structure activity relationships, especially as they related to problems of oral activity. In 1990 he established a highly automated laboratory combining computations and experimental physical property measurements. Experimentally, his laboratory provided experimental solubility measurements on medicinal compounds synthesized at the Pfizer Groton site. Computationally he champions a very pragmatic, chemistry end user oriented, approach to the problem of oral activity improvement. Dr. Lipinski is currently an independent medicinal chemistry consultant working from his home office in Waterford, CT.

He is a member of the Medicinal Chemistry section of the American Chemical Society, the American Association of Pharmaceutical Sciences and the Society for Biomolecular Sciences. He serves on the scientific advisory board of Melior Discovery, The KU Leuven University, Dundee University and MRC Technology UK drug discovery efforts. He is a member of the editorial board of the journal of Pharmaceutical Sciences and the highlights advisory board of Nature Reviews Drug Discovery and the advisory boards of several other journals. He is a member of the Medicinal Chemistry "Hall of Fame", the 2006 recipient of an honorary law degree from the University of Dundee; the Society of Biomolecular Sciences's winner of the 2006 SBS Achievement Award for Innovation in HTS, the American Chemical Society's 2005 winner of the E. B. Hershberg Award for Important Discoveries in Medicinally Active Substances and the 2004 winner of the Division of Medicinal Chemistry Award of the ACS Division of Medicinal Chemistry. He is an adjunct faculty member in Biochemistry at the University of Massachusetts, Amherst, and has over 235 publications and invited presentations and 17 issued US patents.

Chris Lipinski is the author of the "Rule of Five" a simple algorithm for predicting drug compounds likely to show oral activity
The Rule of Five (named because a 5 appears often in the cut-off values, there are actually only 4 rules)

Poor absorption or permeation are more likely when there are:
More than 5 H-bond donors
The MWT is over 500
The CLog P is over 5 (or MLOGP is over 4.15)
The sum of N's and O's is over 10

Substrates for transporters and natural products are exceptions

Reference. "Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings." Christopher A. Lipinski, Franco Lombardo, Beryl W. Dominy, Paul J. Feeney. Advanced Drug Delivery Reviews, 23, 3-25 (1997).

Dr. Lipinski is a scientific advisor to Melior Discovery located in Exton, PA (http://www.meliordiscovery.com). Melior Discovery finds new uses for old drugs through a panel of 30-40 multiplexed in-vivo mouse screens. The screens are completely phenotypic without any mechanistic bias. Hence the target opportunity space is very broad. Lipinski says "The Melior research approach is so attractive because it is how drugs were discovered in the 1970's except that the in-vivo screening is now much more efficient."

Drug Discovery. Expertise in bioisosterism and drug properties required for oral activity