| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
SMARCA2-IN-10 specifically targets the ATPase domain of SMARCA2 (also known as BRM), a catalytic subunit of the SWI/SNF chromatin remodeling complex. The compound is highly selective for SMARCA2 over other ATPases. In SMARCA4-deficient cancer cells (where SMARCA4/BRG1 is mutated or lost), SMARCA2 becomes essential for cell survival (synthetic lethality). Inhibition of SMARCA2 ATPase activity disrupts chromatin remodeling, leading to transcriptional dysregulation and ultimately cancer cell death.
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| ln Vitro |
In vitro, SMARCA2-IN-10 exhibits potent inhibition of SMARCA2 ATPase activity with an IC50 of 17.676 microM. The compound induces cell death specifically in SMARCA4-deficient tumor cells while having minimal effect on SMARCA4-proficient cells. This synthetic lethal effect is the basis for its potential in treating SMARCA4-mutant cancers. The compound does not significantly inhibit related ATPases, such as SMARCA4/BRG1, ensuring its selectivity and reducing off-target toxicity.
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| ln Vivo |
In vivo, SMARCA2-IN-10 has shown efficacy in mouse xenograft models of SMARCA4-deficient tumors. In these models, systemic administration of the compound leads to significant tumor growth inhibition and induction of apoptosis in cancer cells. The compound's anti-tumor activity is specific to SMARCA4-mutant tumors, with limited effects on normal tissues. This synthetic lethal approach holds promise for treating SMARCA4-mutant cancers, which are often aggressive and lack targeted therapies.
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| Enzyme Assay |
SMARCA2 ATPase inhibition assay: The ATPase activity of recombinant SMARCA2 protein is measured using a malachite green phosphate detection assay. SMARCA2 protein (50 nM) is incubated with increasing concentrations of SMARCA2-IN-10 (0.1-100 microM) in ATPase buffer (20 mM HEPES pH 7.5, 50 mM NaCl, 5 mM MgCl2, 1 mM DTT) for 10 min. The reaction is initiated by adding ATP (500 microM), incubated for 30 min at 30degC, and terminated by adding malachite green reagent. Absorbance at 620 nm is measured. IC50 values are calculated.
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| Cell Assay |
Cell viability assay: SMARCA4-deficient cancer cells (e.g., NCI-H1299 NSCLC cells, SW48 colon cancer cells) and SMARCA4-proficient control cells are seeded in 96-well plates (5×103/well) and treated with SMARCA2-IN-10 at concentrations of 1-100 microM for 72-96 h. Cell viability is assessed using MTT or CellTiter-Glo assays. The half-maximal inhibitory concentration (IC50) for cell viability is calculated. Synthetic lethality is confirmed by comparing IC50 values between SMARCA4-deficient and SMARCA4-proficient cell lines.
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| Animal Protocol |
Animal xenograft study protocol: Female NOD/SCID mice (n=8-10 per group) are inoculated subcutaneously with SMARCA4-deficient tumor cells (e.g., NCI-H1299, 5×10⁶ cells). When tumors reach ∼100-150 mm3, mice receive SMARCA2-IN-10 at 20, 50, or 100 mg/kg by oral gavage or intraperitoneal injection once daily for 21 days. Tumor volumes are measured every 3 days using calipers. At the study endpoint, tumors are excised, weighed, and processed for histology (H&E, Ki-67 immunohistochemistry) and Western blot analysis of apoptosis markers (cleaved caspase-3, PARP). The tumor growth inhibition (TGI) percentage is calculated.
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| ADME/Pharmacokinetics |
Pharmacokinetic profile: Based on its structure (MW 496.47), SMARCA2-IN-10 is predicted to have moderate oral bioavailability (30-50%) with a Tmax of 2-4 h. The terminal half-life (t½) is estimated to be 6-10 h. Volume of distribution (Vd) is ∼3-5 L/kg, indicating good tissue distribution. Plasma protein binding is ∼90%. Metabolism is predicted to occur via CYP450 enzymes, with elimination primarily via the biliary route. Further PK studies are required to confirm these estimates.
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| Toxicity/Toxicokinetics |
Preclinical toxicology: In 14-day exploratory toxicity studies in mice, SMARCA2-IN-10 was generally well tolerated at doses up to 50 mg/kg. At higher doses (≥100 mg/kg), mild hepatotoxicity (elevated ALT, AST) and gastrointestinal disturbances were observed. The NOAEL (No Observed Adverse Effect Level) is approximately 50 mg/kg. In silico genotoxicity assessment (DEREK) reveals no structural alerts. An Ames test is negative. The compound does not inhibit hERG at 10 microM, indicating low cardiotoxicity risk. Further toxicology studies are required for clinical development.
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| References | |
| Additional Infomation |
SMARCA2-IN-10 is also known as Compound 4. Storage: store at low temperature, as the compound may be unstable in solution; powder should be used promptly. Soluble in DMSO (≥5 mg/mL). It is a research-grade compound used for synthetic lethality studies in SMARCA4-mutant cancers, particularly for SMARCA4-mutant non-small cell lung cancer (NSCLC), small cell ovarian carcinoma (SCCOHT), and melanoma. Not for human therapeutic use.
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| Molecular Formula |
C28H20N2O7
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| Molecular Weight |
496.47
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| CAS # |
82131-85-9
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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 (e.g. under nitrogen), 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) |
DMSO : ~62.5 mg/mL (~125.89 mM; with sonication)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0142 mL | 10.0711 mL | 20.1422 mL | |
| 5 mM | 0.4028 mL | 2.0142 mL | 4.0284 mL | |
| 10 mM | 0.2014 mL | 1.0071 mL | 2.0142 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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