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

Jianyong Chen; Longchuan Bai; Denzil Bernard; Zaneta Nikolovska-Coleska; Cindy Gomez; Jian Zhang; Han Yi; Shaomeng Wang

doi:10.1021/ml100010j

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

ACS Med Chem Lett. 2010 May 13;1(2):85-89. doi: 10.1021/ml100010j.

Authors

Jianyong Chen¹, Longchuan Bai, Denzil Bernard, Zaneta Nikolovska-Coleska, Cindy Gomez, Jian Zhang, Han Yi, Shaomeng Wang

Affiliation

¹ 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.

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.

Abstract

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