Therapeutics: Baculoviral IAP repeat-containing 2 (BIRC2; cIAP1); inhibitor of apoptosis (IAP); X-linked inhibitor of apoptosis (XIAP)

In vitro and mouse studies identified heterodimeric antagonists of IAP proteins that could help treat cancer. Chemical synthesis and in vitro enzymatic assays identified two lead antagonists that inhibited the BIR2 and BIR3 domains of both cIAP1 and XIAP at IC50 values of 1.5-4.9 nM. In mice bearing xenograft melanoma or lung tumors, two of the antagonists induced complete tumor regression at or below their respective maximum tolerated doses of 15 and 7.5 mg/kg. Next steps could include testing the most potent heterodimeric antagonists in models of other tumor types...