基于结构的构象受限、细胞可渗透的信号转导和转录激活因子3（STAT3）抑制剂设计
Structure-Based Design of Conformationally Constrained, Cell-Permeable STAT3 Inhibitors.
作者信息
Chen Jianyong, Bai Longchuan, Bernard Denzil, Nikolovska-Coleska Zaneta, Gomez Cindy, Zhang Jian, Yi Han, Wang Shaomeng
机构信息
Comprehensive Cancer Center and Departments of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan, 1500 E. Medical Center Dr., Ann Arbor, MI 48109, USA.
出版信息
ACS Med Chem Lett. 2010 May 13;1(2):85-89. doi: 10.1021/ml100010j.
Abstract
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 µM, 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.
摘要
我们在此报告了一类基于结构设计的构象受限、强效、可穿透细胞的小分子抑制剂，其靶向信号转导和转录激活因子3（STAT3）中的Src同源2（SH2）结构域。化合物11（CJ-1383）与STAT3结合，解离常数（K(i)）值为0.95微摩尔，剂量依赖性地抑制细胞STAT3信号传导和癌细胞生长，并在具有组成性激活STAT3的MDA-MB-468癌细胞系中诱导凋亡。
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