Structure-BasedDesignofConformationallyConstrained, Cell-Permeable STAT3 Inhibitors

We report herein the structure-based design of a class of conforma- tionallyconstrained,potent,cell-permeablesmall-moleculeinhibitorstotargetthe SH2 domain in STAT3. Compound 11 (CJ-1383) binds to STAT3 with a Ki 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 constitu- tively activated STAT3.