Structural Insights into the Design of Small Molecule Inhibitors That Selectively Antagonize Mcl-1

被引：53

作者：

Bernardo, Paul H. ^{[1
]}

Sivaraman, Thirunavukkarasu ^{[2
]}

Wan, Kah-Fei ^{[3
]}

Xu, Jin ^{[1
]}

Krishnamoorthy, Janarthanan ^{[2
]}

Song, Chun Meng ^{[4
]}

Tian, Liming ^{[1
]}

Chin, Jasmine S. F. ^{[1
]}

Lim, Diane S. W. ^{[1
]}

Mok, Henry Y. K. ^{[2
]}

Yu, Victor C. ^{[5
]}

Tong, Joo Chuan ^{[4
,6
]}

Chai, Christina L. L. ^{[1
]}

机构：

[1] ASTAR, Inst Chem & Engn Sci, Singapore 627833, Singapore

[2] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore

[3] ASTAR, Ctr Expt Therapeut, Singapore 138669, Singapore

[4] ASTAR, Inst Infocomm Res, Singapore 138632, Singapore

[5] Natl Univ Singapore, Fac Sci, Dept Pharm, Singapore 117543, Singapore

[6] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117597, Singapore

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 53卷 / 05期

关键词：

BH3 MIMETIC ABT-737; APOPTOSIS; PROTEINS; RESISTANCE; REVEALS; POTENT; LIGAND;

D O I：

10.1021/jm901469p

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The screening of a small focused library of rhodanine derivatives as inhibitors of Bcl-2 proteins led to the discovery of two structurally related compounds with different binding profiles against the Bcl-XL and the Mcl-1 proteins. Subsequent NMR studies with Mutant proteins and in silico docking studies provide it possible rationale for the observed specificity.

引用

页码：2314 / 2318

页数：5

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