[CAS NO. 957135-43-2]  SM-164

SM-164 is a non-peptide, cell-permeable, bivalent small-molecule, which mimics Smac protein for targeting XIAP. SM-164 binds to XIAP containing both BIR domains with an IC ₅₀ value of 1.39 nM, being 300 and 7000-times more potent than its monovalent counterparts and the natural Smac AVPI peptide, respectively. SM-164 concurrently interacts with both BIR domains in XIAP and functions as an ultra-potent antagonist of XIAP in both cell-free functional and cell-based assays. SM-164 targets cellular XIAP and effectively induces apoptosis at concentrations as low as 1 nM in leukemia cancer cells, while having a minimal toxicity to normal human primary cells at 10,000 nM ^[1] . The binding affinities of SM-164 to XIAP, cIAP-1, and cIAP-2 proteins are determined using fluorescence-polarization based assays. SM-164 has a K _i value of 0.56 nM to XIAP protein containing both BIR2 and BIR3 domains. SM-164 has a K _i value of 0.31 nM to cIAP-1 protein containing both BIR2 and BIR3 domains. SM-164 binds to cIAP-2 BIR3 protein with K _i values of 1.1 nM. Addition of exogenous TNFα can significantly enhance the activity of these Smac mimetics, especially for SM-164, in resistant cancer cell lines such as HCT116 and MDA-MB-453 ^[2] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.