| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
SMARCA2 (BRM), a catalytic subunit of the SWI/SNF chromatin-remodeling complex. SMD-3040 is a selective SMARCA2 PROTAC degrader with a DC50 of 12 nM and a maximum degradation (Dmax) of 91%. It binds to SMARCA2 and the VHL E3 ligase simultaneously, tagging SMARCA2 with ubiquitin for proteasomal destruction. This mechanism exploits the synthetic lethal relationship in cancers that have lost the paralog, SMARCA4.
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| ln Vitro |
In vitro, SMD-3040 demonstrates potent and selective degradation of SMARCA2 (DC50 = 12 nM) in a variety of cancer cell lines, with minimal effect on its highly related family member SMARCA4. This degradation results in the inhibition of cancer cell proliferation, particularly in SMARCA4-deficient cells. SMD-3040 effectively kills these cancer cells by inducing cell cycle arrest and apoptosis, validating SMARCA2 as a therapeutic target.
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| ln Vivo |
In vivo, SMD-3040 exhibits strong antitumor activity in preclinical xenograft models. In mice bearing SMARCA4-deficient human tumor xenografts, systemic administration of SMD-3040 leads to robust SMARCA2 degradation in the tumor tissue, which correlates with significant tumor growth inhibition or regression. These studies demonstrate the therapeutic potential of SMARCA2 degradation for treating specific cancers, such as non-small cell lung cancer.
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| Enzyme Assay |
A non-cell-based TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer) assay is used to confirm ternary complex formation. VHL protein (His-tagged) and SMARCA2 protein (Flag-tagged) are incubated with increasing concentrations of SMD-3040 (0-10000 nM). Terbium-labeled anti-His and fluorescein-labeled anti-Flag antibodies are added. TR-FRET signal is measured. A positive signal indicates the compound's ability to bridge the E3 ligase and target.
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| Cell Assay |
SMARCA4-deficient non-small cell lung cancer cells (e.g., NCI-H1299) are seeded in 96-well plates. After 24 hours, cells are treated with increasing concentrations of SMD-3040 (0-1000 nM) for 5 days. Cell viability is measured using a CellTiter-Glo assay. For degradation analysis, cells are treated with 0.1-100 nM of the compound for 8-24 h, lysed, and analyzed by Western blotting with SMARCA2 and SMARCA4 antibodies.
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| Animal Protocol |
Female BALB/c nude mice are subcutaneously implanted with SMARCA4-deficient cancer cells. When tumors reach ~150-200 mm3, mice are randomized into groups (n=8-10). SMD-3040 is administered via intraperitoneal injection at doses of 1-30 mg/kg, once daily or every other day, for 3-4 weeks. Tumor volume is measured using calipers every 3 days. At the end of the study, tumors are collected for Western blot analysis of SMARCA2 degradation and downstream pharmacodynamic markers.
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| ADME/Pharmacokinetics |
SMD-3040 is a research compound with a molecular weight of 943.21 and a purity of ≥98%. It is soluble in DMSO at concentrations >100 mg/mL. For in vivo administration, it is typically formulated in a vehicle such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline. PK studies are needed, but it is expected to have a short to moderate half-life (2-6 hours), moderate clearance, and good tissue distribution.
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| Toxicity/Toxicokinetics |
SMD-3040 is for research use only and is not approved for human clinical use. In preclinical toxicology studies in mice, the compound is generally well-tolerated at effective doses, with no significant body weight loss or major organ toxicities reported. Since it targets a chromatin regulator, the primary risk is on-target hematologic toxicity, but selectivity over SMARCA4 may reduce this risk. Standard handling precautions for chemical probes should be followed.
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| References | |
| Additional Infomation |
SMD-3040 (CAS: 3033109-92-8) is a chemical probe used to study the SMARCA2/4 synthetic lethal axis. The compound demonstrates a remarkable balance of high potency (DC50 = 12 nM) and high selectivity for SMARCA2 over SMARCA4. It is not an approved drug but is a valuable research tool. Storage as a powder at -20degC is recommended for long-term stability. It is a PROTAC molecule, not a traditional inhibitor.
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| Molecular Formula |
C52H66N10O5S
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|---|---|
| Molecular Weight |
943.21
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| CAS # |
3033109-92-8
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| Related CAS # |
SMD-3040 TFA;SMD-3040 intermediate-1
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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 |
| 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 :≥ 100 mg/mL (~106.02 mM)
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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 | 1.0602 mL | 5.3010 mL | 10.6021 mL | |
| 5 mM | 0.2120 mL | 1.0602 mL | 2.1204 mL | |
| 10 mM | 0.1060 mL | 0.5301 mL | 1.0602 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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