FSP3: simple and valuable

Abstract

The discovery and development process of innovative drug requires a shocking amount of money and time due in part to the high attrition rate of drug candidates in development. The most prominent cause of the failures was associated with poor pharmacokinetic and ADME (absorption, distribution, metabolism and elimination) properties. Thus, these features should be measured at the early stages of drug design using structural physicochemical parameters of molecules including computational calculations. Most of modern discovery hits extremely suffer from a lack of three-dimensional shape. Oppositely, natural products have “advanced” 3D-shapes and demonstrate exquisite action on very specific biotargets. Molecule nonplanarity could be characterized by “fraction of sp3-hybridized carbons (Fsp3)”, i.e. number of sp3-hybridized/total carbon counts.