PMID: 12769701May 29, 2003Paper

Role of ADME characteristics in drug discovery and their in silico evaluation: in silico screening of chemicals for their metabolic stability

Current Topics in Medicinal Chemistry
Vijay K GombarZhiyang Zhao

Abstract

Drug discovery is a long, arduous process broadly grouped into disease target identification, target validation, high-throughput identification of "hits" and "leads", lead optimization, and pre-clinical and clinical evaluation. Each area is a vast discipline in itself. However, all but the first two stages involve, to varying degrees, the characterization of absorption, distribution, metabolism, excretion, (ADME), and toxicity (T) of the molecules being pursued as potential drug candidates. Clinical failures of about 50% of the Investigational New Drug (IND) filings are attributed to their inadequate ADMET attributes. It is, therefore, no surprise that, in the current climate of social and regulatory pressure on healthcare costs, the pharmaceutical industry is searching for any means to minimize this attrition. Building mathematical models, called in silico screens, to reliably predict ADMET attributes solely from molecular structure is at the heart of this effort in reducing costs as well as development cycle times. This article reviews the emerging field of in silico evaluation of ADME characteristics. For different approaches that have been employed in this area, a critique of the scope and limitations of their descriptors, ...Continue Reading

Citations

Sep 10, 2003·Drug Discovery Today·Hongshi Yu, Adedayo Adedoyin
Jan 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Moo-Yeal LeeDouglas S Clark
Jun 25, 2010·Journal of Toxicology and Environmental Health. Part B, Critical Reviews·Daniel KrewskiLauren Zeise
Oct 9, 2007·Journal of Pharmaceutical Sciences·Yoshihisa Shirasaki
Mar 5, 2004·Journal of Pharmaceutical Sciences·Vijay K GombarCosette S Serabjit-Singh
Mar 29, 2011·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·F MaestrelliP Mura
Nov 3, 2010·Toxicology and Applied Pharmacology·Patricia RuizVijay Gombar
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Jul 21, 2020·Journal of Biomolecular Structure & Dynamics·Jitendra Subhash RaneShashikant Ray
Dec 4, 2020·Drug Design, Development and Therapy·Charlaine A AventuradoAgnes L Castillo
Mar 5, 2013·Journal of Chemical Information and Modeling·Vijay K Gombar, Stephen D Hall

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