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Development of a cell viability assay to assess drug metabolite structure-toxicity relationships.

Abstract：

:Many adverse drug reactions are caused by the cytochrome P450 (CYP)-dependent activation of drugs into reactive metabolites. In order to reduce attrition due to metabolism-induced toxicity and to improve the safety of drug candidates, we developed a simple cell viability assay by combining a bioactivation system (human CYP3A4, CYP2D6 and CYP2C9) with Hep3B cells. We screened a series of drugs to explore structural motifs that may be responsible for CYP450-dependent activation caused by reactive metabolite formation, which highlighted specific liabilities regarding certain phenols and anilines.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Rana P,Will Y,Nadanaciva S,Jones LH

doi

10.1016/j.bmcl.2016.06.088

subject

Has Abstract

pub_date

2016-08-15 00:00:00

pages

4003-6

issue

16

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(16)30699-0

journal_volume

26

pub_type

杂志文章

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