Background:

SM-164 is a bivalent mimetic of Smac with Ki values of 0.31 nM, 1.1 nM and 0.56 nM for cIAP-1, cIAP-2 and XIAP, respectively¹.

SM-164 is developed as an anticancer agent. It plays its antitumor roles through inducing degradation of cellular inhibitor of apoptosis protein (cIAP)-1/2, antagonizing X-linked inhibitor of apoptosis protein (XIAP) and inducing TNFα–dependent apoptosis in tumor cells. SM-164 is a bivalent mimetic containing two SM-122 analogues. It binds to cIAP-1 protein containing bothBIR2 and BIR3 domains, cIAP-2 BIR3 protein and XIAP protein containing both BIR2 and BIR3 domains with Ki values of 0.31 nM, 1.1 nM and 0.56 nM, respectively. In tumor cells, treatment of SM-164 significantly reduced cIAP-1 level to undetectable levels (1nM, 60min), effectively antagonized cellular XIAP and enhanced TNFα secretion. In the MDA-MB-231 xenograft model, administration of SM-164 at dose of 5mg/kg markedly decreased cIAP-1 level within 1 hour and activated caspase-8, caspase-9 and caspase-3 at 3 hour¹.

参考文献:
1.?Lu J, Bai L, Sun H, et al. SM-164: a novel, bivalent Smac mimetic that induces apoptosis and tumor regression by concurrent removal of the blockade of cIAP-1/2 and XIAP. Cancer research, 2008, 68(22): 9384-9393.