Compound 402112

Compound 402112 is a small molecule inhibitor of the X-linked inhibitor of apoptosis protein (XIAP), identified through ligand-based virtual screening of the University of Cincinnati's Drug Discovery Center Library. It was designed to mimic the AVPI tetrapeptide motif of the second mitochondria-derived activator of caspase (SMAC), which naturally binds to the BIR3 domain of XIAP to relieve its inhibition of caspases. In preclinical studies, Compound 402112 demonstrated anti-proliferative activity against human melanoma (A375, MDA-MB-435) and prostate cancer (PC-3, LNCap) cell lines, with IC50 values ranging from 650 nM to 2.5 μM. It effectively activates caspase-9, suggesting its potential as a therapeutic agent to overcome apoptosis resistance in malignancies.