| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
cIAP-1 0.31 nM (Ki) cIAP-2 1.1 nM (Ki) cIAP
XIAP (X-linked inhibitor of apoptosis protein), specifically binding to both the BIR2 and BIR3 domains with an IC50 value of 1.39 nM. SM-164 Hydrochloride is 300 and 7000 times more potent than its monovalent counterparts and the natural Smac AVPI peptide, respectively. It also targets cIAP-1 (Ki=0.31 nM) and cIAP-2 (Ki=1.1 nM). |
|---|---|
| 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].
In vitro, SM-164 Hydrochloride is a potent Smac mimetic that binds to XIAP with high affinity (IC50=1.39 nM). It shows strong antiproliferative activity against various cancer cell lines and is highly synergistic with TRAIL in both TRAIL-sensitive and TRAIL-resistant cancer cells of breast, prostate, and colon cancer. The compound effectively promotes apoptosis by antagonizing IAP function. |
| 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].
In vivo, SM-164 Hydrochloride is highly effective in inhibiting tumor growth and can achieve tumor regression in xenograft models. In the MDA-MB-231 xenograft model, treatment with SM-164 at 1 mg/kg completely inhibits tumor growth. The compound shows good efficacy when used alone or in combination with other therapeutic agents such as TRAIL in various cancer models. |
| Enzyme Assay |
XIAP binding assay protocol: XIAP protein containing both BIR2 and BIR3 domains is incubated with increasing concentrations of SM-164 Hydrochloride (0-1000 nM) in binding buffer. Fluorescence polarization is measured using a labeled Smac peptide probe. The IC50 of 1.39 nM is determined by measuring displacement of the probe and calculated using non-linear regression analysis. Each concentration is measured in triplicate.
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| Cell Assay |
Cell proliferation assay protocol: Cancer cells (MDA-MB-231, PC-3, HCT-116) are seeded in 96-well plates at 5,000 cells/well and treated with SM-164 Hydrochloride at concentrations ranging from 0-1000 nM for 72 hours. Cell viability is assessed using MTT or CCK-8 assay. For synergy studies, SM-164 is combined with TRAIL (0-100 ng/mL), and the combination index is calculated using the Chou-Talalay method. Apoptosis is measured by flow cytometry using Annexin V-FITC/PI staining.
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| Animal Protocol |
Xenograft tumor model protocol: Female BALB/c nude mice (6-8 weeks old) are subcutaneously implanted with MDA-MB-231 cells (5×10⁶ cells/mouse). When tumors reach ~100-150 mm3, mice are randomized into groups (n=8). SM-164 Hydrochloride is administered via intraperitoneal injection at 0.5-1 mg/kg, once daily for 14-21 days. Tumor volume is measured every 2-3 days using a caliper. Tumor growth inhibition (TGI%) is calculated. Tumors are excised for TUNEL and immunohistochemistry analysis.
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| ADME/Pharmacokinetics |
PK studies in rodents (example): Male SD rats receive a single intravenous or intraperitoneal dose of SM-164 Hydrochloride at 1-5 mg/kg. Blood samples are collected at multiple time points (0, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose). Plasma concentrations are measured by LC-MS/MS. PK parameters including half-life, Cmax, AUC, clearance, and volume of distribution are calculated using non-compartmental analysis.
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| Toxicity/Toxicokinetics |
Toxicity data for SM-164 Hydrochloride are limited in published literature. As a potent apoptosis inducer, potential toxicities may include off-target effects on normal proliferating tissues. In preclinical studies at therapeutic doses (1 mg/kg in mice), the compound generally shows acceptable tolerability. The compound is intended for research use only and has not been approved for human therapeutic applications. Standard safety precautions should be observed.
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| References |
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| Additional Infomation |
SM-164 Hydrochloride is a research compound that has not entered clinical trials or received regulatory approval for human use. It represents a second-generation Smac mimetic with significantly improved potency compared to earlier compounds. SM-164 has been studied extensively in combination with TRAIL and other anticancer agents for synergistic effects. The compound is water-soluble (10 mM in water) and should be stored desiccated at -80degC for long-term stability.
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| Molecular Formula |
C62H85CLN14O6
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|---|---|
| Molecular Weight |
1157.88
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| CAS # |
2734174-02-6
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| Related CAS # |
SM-164;957135-43-2
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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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