期刊
MINI-REVIEWS IN MEDICINAL CHEMISTRY
卷 9, 期 6, 页码 703-716出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138955709788452694
关键词
Drug metabolism; toxicology; lead optimization; drug discovery; oral bioavailability; half-life; ADME
The lead optimization paradigm includes a team of experts that has a multitude of parameters to consider when moving from an initial lead compound through the lead optimization phase to the development phase. While in the past the team may have had only a medicinal chemist and a pharmacologist, the current team would often include experts in the areas of drug metabolism and pharmacokinetics (DMPK) as well as chemical toxicity. This review provides an overview of the some of the recent advances in the areas of DMPK screening plus a discussion of some of the assays that can be used to begin to screen for toxicity issues. The focus of this review is the major potential problem areas: oral bioavailability, half-life, drug-drug interactions and metabolism and toxicity issues.
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