A Comparison of Physiochemical Property Profiles of Development and Marketed Oral Drugs

TLDR

Drug discovery imposes strict selection pressures, and marketed oral drugs typically exhibit favorable physiochemical properties for absorption, metabolism, distribution, and clearance. This paper compares the distributions of physiochemical properties of oral drugs at different clinical development phases to those already marketed, aiming to identify trends that favor successful passage to market. The study constructed two libraries—one of oral drugs in development and one of marketed oral drugs—to enable comparative analysis. Analysis revealed that mean molecular weight of development‑phase oral drugs decreases and converges toward the marketed mean, while the most lipophilic compounds are being discontinued.

Abstract

The process of drug discovery applies rigorous selection pressures. Marketed oral drugs will generally possess favorable physiochemical properties with respect to absorption, metabolism, distribution, and clearance. This paper describes a study in which the distributions of physiochemical properties of oral drugs in different phases of clinical development are compared to those already marketed. The aim is to identify the trends in physiochemical properties that favor a drug's successful passage through clinical development and on to the market. Two libraries were created, one of current development oral drugs and one of marketed oral drugs. Statistical analysis of the two showed that the mean molecular weight of orally administered drugs in development decreases on passing through each of the different clinical phases and gradually converges toward the mean molecular weight of marketed oral drugs. It is also clear that the most lipophilic compounds are being discontinued from development.