A non-peptidomimetic inhibitor of IAP protein-peptide interactions
ASTX660 is an inhibitor of inhibitor of apoptosis (IAP) protein-peptide interactions.1 It inhibits the protein-peptide interaction between the IAP1 and XIAP BIR3 domains with a Smac-derived peptide in cell-free assays (IC50s = <40 and 12 nM, respectively). ASTX660 inhibits the protein-protein interaction between XIAP and caspase-9 in HEK293 cells (EC50 = 2.8 nM) and induces displacement of Smac from XIAP in A375 melanoma cells. It induces apoptosis in MDA-MB-231, A375, and SK-MEL-28 cells in a TNF-α-dependent manner. In vivo, ASTX660 (20 mg/kg) reduces tumor growth in MDA-MB-231 breast cancer and A375 melanoma mouse xenograft models.
1.Ward, G.A., Lewis, E.J., Ahn, J.S., et al.ASTX660, a novel non-peptidomimetic antagonist of cIAP1/2 and XIAP, potently induces TNFα-dependent apoptosis in cancer cell lines and inhibits tumor growthMol. Cancer Ther.17(7)1381-1391(2018)
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