Blobs of hope and other flights of fancy

presentation · 11 years ago
by Steven W. Muchmore (Abbott Laboratories)
Calculator Plugins (logP logD pKa etc...)

Simplification of abstract or complex information to a simple principle or rule of thumb is a common way to make the information more concise and accessible to daily use. In pharmaceutical development, several rules of thumb have been developed, based on analyses of trends in data that are used to increase the likelihood that a compound will have acceptable chemical properties going forward from lead optimization to pre-clinical and clinical development. Examples of these rules are Lipinski’s Rule of 5 and associated Rules of 4, 6 and 7 to predict solubility and permeability, Golden Triangle for oral bioavailability, the Rule of 3/75 for blood brain barrier penetration, and fSP3 and 3 or fewer aromatic rings for general develop-ability. While useful, rules of thumb can be misleading, in some cases imparting too few details about underlying trends in datasets. Alternative approaches which give a sense of the probability of success can be developed without requiring additional data to be generated.