Discovery of a Class of Novel Tankyrase Inhibitors that Bind to Both the Nicotinamide Pocket and the Induced Pocket

被引：45

作者：

Bregman, Howard ^{[1
]}

Gunaydin, Hakan ^{[2
]}

Gu, Yan ^{[2
]}

Schneider, Steve ^{[2
]}

Wilson, Cindy ^{[3
]}

DiMauro, Erin F. ^{[1
]}

Huang, Xin ^{[2
]}

机构：

[1] Amgen Inc, Dept Med Chem, Cambridge, MA 02142 USA

[2] Amgen Inc, Dept Mol Struct & Characterizat, Cambridge, MA 02142 USA

[3] Amgen Inc, Therapeut Innovat Unit, Cambridge, MA 02142 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 56卷 / 03期

关键词：

SMALL-MOLECULE INHIBITORS; POLY(ADP-RIBOSE) POLYMERASE; STRUCTURAL BASIS; COMPLEX;

D O I：

10.1021/jm301607v

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Potent and selective inhibitors of tankyrases have recently been characterized to bind to an induced pocket. Here we report the identification of a novel potent and selective tankyrase inhibitor that binds to both the nicotinamide pocket and the induced pocket. The crystal structure of human TNKS1 in complex with this "dual-binder" provides a molecular basis for their strong and specific interactions and suggests clues for the further development of tankyrase inhibitors.

引用

页码：1341 / 1345

页数：5

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