GDC-0152

GDC-0152 is a small-molecule IAP antagonist that triggers tumor cell apoptosis by selectively antagonizing IAPs. GDC-0152 binds to the XIAP BIR3 domain, the BIR domain of ML-IAP, and the BIR3 domains of cIAP1 and cIAP2 with K(i) values of 28, 14, 17, and 43 nM, respectively. GDC-0152 inhibits tumor growth when dosed orally in the MDA-MB-231 breast cancer xenograft model. GDC-0152 induces activation of caspase-3/7, and lead to decreased viability of breast cancer cells without affecting normal mammary epithelial cells. GDC-0152 induces NF-κB transcriptional activity leading to expression of several chemokines and cytokines, of which tumor necrosis factor alpha (TNF-α) is the most important for single-agent tumor activity.