| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
cIAP-1 0.31 nM (Ki) cIAP-2 1.1 nM (Ki) cIAP
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|---|---|
| ln Vitro |
SM-164 is a bivalent, non-peptide, cell-permeable small molecule that targets XIAP by imitating the Smac protein. With an IC50 value of 1.39 nM, SM-164 binds to XIAP that contains both BIR domains. This binding is 300 and 7000 times more effective than the native Smac AVPI peptide and its monovalent equivalents, respectively. In both cell-free functional and cell-based experiments, SM-164 acts as an ultra-potent antagonist of XIAP while concurrently interacting with both of the BIR domains in XIAP. Targeting cellular XIAP, SM-164 efficiently induces apoptosis in leukemia cancer cells at doses as low as 1 nM, with just a negligible amount of damage to normal human primary cells at 10,000 nM[1]. Using fluorescence-polarization based assays, the binding affinities of SM-164 to XIAP, cIAP-1, and cIAP-2 proteins are ascertained. The Ki value of SM-164 to the XIAP protein, which possesses both BIR2 and BIR3 domains, is 0.56 nM. The Ki value of SM-164 to the cIAP-1 protein, which possesses both BIR2 and BIR3 domains, is 0.31 nM. At 1.1 nM, SM-164 binds to the cIAP-2 BIR3 protein. Exogenous TNFα can greatly increase the effectiveness of these Smac mimetics in resistant cancer cell lines like HCT116 and MDA-MB-453, particularly for SM-164[2].
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| ln Vivo |
It is determined whether SM-164 can stop tumor growth. SM-164 has demonstrated remarkable efficacy in suppressing tumor development and achieving tumor remission in the MDA-MB-231 xenograft model. SM-164 medication at a dose of 1 mg/kg totally stops tumor development while the patient is receiving treatment. The tumor volume decreases by 65% when treated with SM-164 at a dose of 5 mg/kg; it starts the treatment on day 25 and ends on day 36, measuring 54±32 mm3. SM-164 exhibits potent anticancer action that is persistent rather than ephemeral. When the tumor size in the control group exceeds 750 mm3 (P<0.02) or at the end of the treatment (P<0.01), SM-164 at 5 mg/kg is statistically more effective than Taxotere[2].
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| References |
[1]. Sun H, et al. Design, synthesis, and characterization of a potent, nonpeptide, cell-permeable, bivalent Smac mimetic that concurrently targets both the BIR2 and BIR3 domains in XIAP. J Am Chem Soc. 2007 Dec 12;129(49):15279-94.
[2]. Lu J, 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 Res. 2008 Nov 15;68(22):9384-93. |
| Molecular Formula |
C62H85CLN14O6
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|---|---|
| Molecular Weight |
1157.88
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| Related CAS # |
SM-164;957135-43-2
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O :≥ 106 mg/mL (~91.55 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 50 mg/mL (43.18 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8636 mL | 4.3182 mL | 8.6365 mL | |
| 5 mM | 0.1727 mL | 0.8636 mL | 1.7273 mL | |
| 10 mM | 0.0864 mL | 0.4318 mL | 0.8636 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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