A novel small-molecule inhibitor of IL-6 signalling

作者：Zinzalla Giovanna; Haque Mohammad R; Basu B Piku; Anderson John; Kaye Samantha L; Haider Shozeb; Hasan Fyeza; Antonow Dyeison; Essex Samantha; Rahman Khondaker M; Palmer Jonathan; Morgenstern Daniel; Wilderspin Andrew F; Neidle Stephen; Thurston David E^*

来源：Bioorganic & Medicinal Chemistry Letters, 2010, 20(23): 7029-7032.

DOI：10.1016/j.bmcl.2010.09.117

• Small molecule
• IL-6 signalling
• Inhibitor
• STAT3

A small library of pyrrolidinesulphonylaryl molecules has been synthesized via an efficient 4-step route, and members evaluated for their ability to inhibit IL-6 signalling. One molecule (6a) was found to have promising activity against IL-6/STAT3 signalling at the low micromolar level, and to selectively inhibit phosphorylation of STAT3 (but not STAT1) in IL-6 stimulated MDA-MB-231 breast cancer and HeLa cell lines. It was also selectively cytostatic in MDA-MB-231 (STAT3-dependent) versus A4 (STAT3-null) cells suggesting STAT3-specific inhibitory properties.

• 出版日期2010-12-1