AT-101

AT-101 (R-(-)-gossypol acetic acid) is a polyphenolic compound isolated from cottonseeds. AT-101 induces Apoptosis through activation of caspase-9, -3, and -7 in VCaP cells. It inhibits Bcl-2 by acting as a BH3 mimetic and disrupts the heterodimerization of Bcl-2 with proapoptotic family members. AT-101 was found to mimic the proapoptosis proteins and is able to bind to the BH3 domains of Bcl-2, Mcl-1, and Bcl-xL. AT-101 has been shown to be therapeutically active as a single agent in several mouse models including breast, prostate, colon, and non-small cell lung cancer. We demonstrate that AT-101 administration delays the onset of androgen-independent prostate cancer in vivo. The use of AT-101 and ADT may further delay the onset of AI disease, resulting in prolonged progression-free survival of prostate cancer.