Structure-Based Design of Conformationally Constrained, Cell-Permeable STAT3 Inhibitors

被引：79

作者：

Chen, Jianyong

Bai, Longchuan

Bernard, Denzil

Nikolovska-Coleska, Zaneta

Gomez, Cindy

Zhang, Jian

Yi, Han

Wang, Shaomeng ^{[1
]}

机构：

[1] Univ Michigan, Ctr Comprehens Canc, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2010年 / 1卷 / 02期

关键词：

STAT3; inhibitor; SH2; domain; apoptosis; SOLID-PHASE SYNTHESIS; SIGNAL TRANSDUCER; SMALL-MOLECULE; PEPTIDOMIMETIC INHIBITORS; SH2; DOMAIN; DIMERIZATION; ACTIVATOR; TARGETS; BINDING; PHOSPHOPEPTIDES;

D O I：

10.1021/ml100010j

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report herein the structure-based design of a class of conformationally constrained, potent, cell-permeable small-molecule inhibitors to target the SH2 domain in STAT3. Compound 11 (CJ-1383) binds to STAT3 with a K-i value of 0.95 mu M, dose-dependently inhibits cellular STAT3 signaling and cancer cell growth, and induces apoptosis in the MDA-MB-468 cancer cell line with constitutively activated STAT3.

引用

页码：85 / 89

页数：5

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