Preliminary SAR study on a novel inhibitor of the apoptosis suppressor Bcl proteins

Proc Amer Assoc Cancer Res, Volume 46, 2005 1207 GX15 is a naturally occuring substance that was recently reported to be a novel inhibitor of the Bcl-2 family of apoptosis suppressor proteins. Furthermore, it exhibited cytotoxicity in several cancer cell lines. Structure-activity-relationship (SAR) studies were initiated by preparing semi-synthetic derivatives from the natural product and by total synthesis. A series of structurally simple analogs of GX15 was found to be potently cytotoxic in vitro. A good inhibitory profile towards Bcl antiapoptotic proteins was obtained with several analogs.