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Journal Article
Review
Stereochemical considerations in pharmacokinetic processes of representative antineoplastic agents.
Drug Metabolism Reviews 2017 November
The vast majority of chemical drugs or drug candidates contain stereocenter(s) in their molecular structures. In these molecules, stereochemical properties are vital properties that influence or even determine their drug actions. Therefore, studying the stereochemical issues of drugs (or drug candidates) is necessary for rational drug use. These stereochemical issues are usually involved with the stereoselectivity in pharmacokinetic processes, especially in the metabolism process. Thus, the investigation of the stereochemical issues in drug metabolism process deserves great attention, especially in those chiral/prochiral antineoplastic agents exhibiting pharmacodynamics and toxicologic differences between stereoisomers. Published reviews concerning this certain issue are inspiring, however they were covering all drug types and only limited antineoplastic drugs were discussed. Here in this review, the research on stereochemical issues in pharmacokinetic processes of some representative antineoplastic agents were described, especially focusing on some newly developed compounds. We highlight the chemical transformations in pharmacokinetic processes of these chiral/prochiral compounds and discuss their different behaviors with metabolic enzymes or transporter proteins, to explicate the observed stereoselectivity intrinsically.
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