Tanner C Reese, Anvita Devineni, Tristan Smith, Ismail Lalami, Jung-Mo Ahn, Ganesh V Raj
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Evaluating physiochemical properties of FDA-approved orally administered drugs.
Introduction: Analyses of orally administered FDA-approved drugs from 1990 to 1993 enabled the identification of a set of physiochemical properties known as Lipinski's Rule of Five (Ro5). The original Ro5 and extended versions still remain the reference criteria for drug development programs. Since many bioactive compounds do not conform to the Ro5, we validated the relevance of and adherence to these rulesets in a contemporary cohort of FDA-approved drugs.
Areas covered: The authors noted that a significant proportion of FDA-approved orally administered parent compounds from 2011 to 2022 deviate from the original Ro5 criteria (~38%) or the Ro5 with extensions (~53%). They then evaluated if a contemporary Ro5 criteria (cRo5) could be devised to better predict oral bioavailability. Furthermore, they discuss many case studies showcasing the need for and benefit of increasing the size of certain compounds and cover several evolving strategies for improving oral bioavailability.
Expert opinion: Despite many revisions to the Ro5, the authors find that no single proposed physiochemical rule has universal concordance with absolute oral bioavailability. Innovations in drug delivery and formulation have dramatically expanded the range of physicochemical properties and the chemical diversity for oral administration.
期刊介绍:
Expert Opinion on Drug Discovery (ISSN 1746-0441 [print], 1746-045X [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on novel technologies involved in the drug discovery process, leading to new leads and reduced attrition rates. Each article is structured to incorporate the author’s own expert opinion on the scope for future development.
The Editors welcome:
Reviews covering chemoinformatics; bioinformatics; assay development; novel screening technologies; in vitro/in vivo models; structure-based drug design; systems biology
Drug Case Histories examining the steps involved in the preclinical and clinical development of a particular drug
The audience consists of scientists and managers in the healthcare and pharmaceutical industry, academic pharmaceutical scientists and other closely related professionals looking to enhance the success of their drug candidates through optimisation at the preclinical level.