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Identification of the Metabolic Profile of the α-Tubulin-Binding Natural Product (-)-Pironetin.

Abstract：

:Pironetin, the only crystallographically confirmed natural product to target α-tubulin, displays potent cytotoxic activity against sensitive and resistant A2780 ovarian cancer cell lines but is only marginally active in vivo. We now report that pironetin has a short half-life (<7 min) in human liver microsomes, suggesting that its limited in vivo efficacy is due to rapid metabolism. Further, we describe the discovery of epoxypironetin as pironetin's major metabolite in human liver microsomes.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Coulup SK,Huang DS,Wong HL,Georg GI

doi

10.1021/acs.jmedchem.8b01774

subject

Has Abstract

pub_date

2019-02-14 00:00:00

pages

1684-1689

issue

3

eissn

0022-2623

issn

1520-4804

journal_volume

62

pub_type

杂志文章

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