Structure-Based Design of Conformationally Constrained, Cell-Permeable STAT3 Inhibitors.
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.
Chen
Jianyong
J
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.
Bai
Longchuan
L
Bernard
Denzil
D
Nikolovska-Coleska
Zaneta
Z
Gomez
Cindy
C
Zhang
Jian
J
Yi
Han
H
Wang
Shaomeng
S