Design and synthesis of a new, conformationally constrained, macrocyclic small-molecule inhibitor of STAT3 via 'click chemistry'

被引：54

作者：

Chen, Jianyong

Nikolovska-Coleska, Zaneta

Yang, Chao-Yie

Gomez, Cindy

Gao, Wei

Krajewski, Krzysztof

Jiang, Sheng

Roller, Peter

Wang, Shaomeng ^{[1
]}

机构：

[1] Univ Michigan, Dept Internal Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Pharmacol & Med Chem, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

[3] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 14期

关键词：

STAT3; conformationally; constrained mimetic; click chemistry; CANCER; TARGETS;

D O I：

10.1016/j.bmcl.2007.04.096

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

STAT3 is a promising molecular target for the design of new anticancer drugs. In this paper, we report the design and synthesis of a conformationally constrained macrocyclic peptidomimetic 2 via click chemistry. Compound 2 was determined to bind to STAT3 with a K, value of 7.3 mu M in a competitive fluorescence-polarization-based binding assay, representing a promising initial lead compound for further optimization. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：3939 / 3942

页数：4

共 13 条

[1] Three-dimensional structure of the Stat3β homodimer bound to DNA [J].