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

被引：10

作者：

Coulup, Sara K. ^{[1
,2
]}

Huang, David S. ^{[1
,2
]}

Wong, Henry L. ^{[1
,2
]}

Georg, Gunda I. ^{[1
,2
]}

机构：

[1] Univ Minnesota, Dept Med Chem, 717 Delaware St SE, Minneapolis, MN 55414 USA

[2] Univ Minnesota, Inst Therapeut Discovery & Dev, 717 Delaware St SE, Minneapolis, MN 55414 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2019年 / 62卷 / 03期

关键词：

PIRONETIN ANALOGS; CANCER; GROWTH; MICROTUBULES; INHIBITION; PREDICTION; DESIGN; TARGET; AGENTS; DRUGS;

D O I：

10.1021/acs.jmedchem.8b01774

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Pironetin, the only crystallographically confirmed natural product to target a-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.

引用

页码：1684 / 1689

页数：6

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