SM-164

SKU: orb1219686

Description

SM-164 binds to XIAP protein containing both the BIR2 and BIR3 domains (IC50: 1.39 nM). It acts as an extremely potent antagonist of XIAP. SM-164 binds to XIAP being 300 and 7000-times more potent than its monovalent counterparts and the natural Smac AVPI peptide, respectively. The binding affinities of SM-164 to XIAP, cIAP-1, and cIAP-2 proteins are determined using fluorescence-polarization based assays. 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 minimal toxicity to normal human primary cells at 10,000 nM. SM-164 has a Ki value of 0.56 nM to XIAP protein containing both BIR2 and BIR3 domains. SM-164 has a Ki value of 0.31 nM to a cIAP-1 protein containing both BIR2 and BIR3 domains. SM-164 binds to cIAP-2 BIR3 protein with Ki values of 1.1 nM.SM-164 is highly effective in the inhibition of tumor growth and capable of achieving tumor regression in the MDA-MB-231 xenograft model. SM-164 (1 mg/kg) treatment fully inhibits tumor growth during the treatment. SM-164 (5 mg/kg) treatment reduces the tumor volume from 147±54 mm3 at the beginning of the treatment (day 25) to 54±32 mm3 at the end of the treatment (day 36), a reduction of 65%. The strong antitumor activity by SM-164 is long-lasting and not transient. SM-164 (5 mg/kg) is statistically more effective than Taxotere at the end of the treatment (P<0.01) or when the tumor size in the control group reached 750 mm3 (P<0.02).

Key Properties

• CAS Number: 957135-43-2
• MW: 1121.42
• Purity: >98% (HPLC)
• Formula: C₆₂H₈₄N₁₄O₆
• SMILES: [H][C@]12CC[C@H](N1C(=O)[C@H](CCCC2)NC(=O)[C@H](C)NC)C(=O)N[C@H](c1cn(CCCCc2ccc(CCCCn3cc(nn3)[C@@H](NC(=O)[C@@H]3CC[C@]4([H])CCCC[C@H](NC(=O)[C@H](C)NC)C(=O)N34)c3ccccc3)cc2)nn1)c1ccccc1
• Target: IAP
• Solubility: DMSO:5.2 mg/mL (4.64 mM; Need ultrasonic)

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

IAP