Probing Mechanisms of CYP3A Time-Dependent Inhibition Using a Truncated Model System.
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ABSTRACT:
SUBMITTER: Wang X
PROVIDER: S-EPMC4538442 | biostudies-literature | 2015 Aug
REPOSITORIES: biostudies-literature
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Probing Mechanisms of CYP3A Time-Dependent Inhibition Using a Truncated Model System.
Wang Xiaojing X Sun Minghua M New Connie C Nam Spencer S Blackaby Wesley P WP Hodges Alastair J AJ Nash David D Matteucci Mizio M Lyssikatos Joseph P JP Fan Peter W PW Tay Suzanne S Chang Jae H JH
ACS medicinal chemistry letters 20150712 8
Time-dependent inhibition (TDI) of cytochrome P450 (CYP) enzymes may incur serious undesirable drug-drug interactions and in rare cases drug-induced idiosyncratic toxicity. The reactive metabolites are often generated through multiple sequential biotransformations and form adducts with CYP enzymes to inactivate their function. The complexity of these processes makes addressing TDI liability very challenging. Strategies to mitigate TDI are therefore highly valuable in discovering safe therapies t ...[more]
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