| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
SMARCA2 (BRM), an ATPase subunit of the SWI/SNF chromatin-remodeling complex. SMD-3040 TFA is a selective degrader of SMARCA2. It binds to SMARCA2 and simultaneously recruits a VHL E3 ubiquitin ligase, tagging the target protein with ubiquitin and leading to its destruction by the proteasome. It shows high selectivity for SMARCA2 over its paralog SMARCA4 (BRG1).
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| ln Vitro |
In vitro, SMD-3040 TFA is a potent SMARCA2 degrader, with a DC50 (half-maximal degradation concentration) of 12 nM and a maximum degradation (Dmax) of 91%. It effectively inhibits the proliferation of cancer cells, particularly those dependent on SMARCA2 for survival, such as SMARCA4-deficient cancers. This degradation leads to robust anti-proliferative effects and cell death, demonstrating a synthetic lethal relationship.
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| ln Vivo |
In vivo, SMD-3040 TFA exhibits strong tumor growth inhibition in xenograft models. Systemic administration leads to significant regression of tumors that are dependent on SMARCA2. These in vivo efficacy studies validate SMARCA2 degradation as a therapeutic strategy for certain cancers, particularly those with loss of SMARCA4, making SMD-3040 a valuable tool for preclinical proof-of-concept studies.
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| Enzyme Assay |
A non-cell-based TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer) assay can confirm ternary complex formation. VHL protein (His-tagged) and SMARCA2 protein (Flag-tagged) are incubated with increasing concentrations of SMD-3040 TFA (0-10000 nM). A terbium-labeled anti-His antibody and a fluorescein-labeled anti-Flag antibody are added. TR-FRET signal is measured, indicating the ability of the compound to bridge the E3 ligase and target protein.
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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 h, cells are treated with increasing concentrations of SMD-3040 TFA (0-1000 nM) for 24-72 hours. Cell viability is assessed using a CellTiter-Glo assay. For degradation analysis, cells are treated with 1-100 nM of the compound for 6-24 h, lysed, and analyzed by Western blotting with SMARCA2 and SMARCA4 antibodies.
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| Animal Protocol |
Female BALB/c nude mice (6-8 weeks old) are subcutaneously implanted with SMARCA4-deficient cancer cells (e.g., NCI-H1299) at 5 × 10⁶ cells per mouse. Once tumors reach ~150 mm3, mice are randomized into groups (n=8-10). SMD-3040 TFA is administered via intraperitoneal injection at doses of 1-30 mg/kg, daily or every other day, for 14-21 days. Tumor volume is measured every 2-3 days, and tumor growth inhibition (TGI) is calculated.
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| ADME/Pharmacokinetics |
SMD-3040 TFA is a PROTAC with a molecular weight of 943.21 (free base). As a TFA salt, it has good solubility in DMSO and is typically formulated in DMSO/PEG300/Tween-80/saline for in vivo administration. PK properties likely include a short to moderate half-life (2-6 h in rodents), moderate clearance, and good tissue distribution. The TFA salt enhances aqueous solubility for both in vitro and in vivo use.
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| Toxicity/Toxicokinetics |
SMD-3040 TFA is a research compound and is not approved for human use. In preclinical xenograft studies, it is generally well-tolerated at effective doses (e.g., 10-30 mg/kg, i.p.), with no significant body weight loss or gross signs of toxicity reported. As a protein degrader, potential off-target degradation is a concern, but selectivity for SMARCA2 over SMARCA4 is high, indicating a low risk of on-target hematological toxicity.
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| References | |
| Additional Infomation |
SMD-3040 TFA is a potent and selective SMARCA2 PROTAC degrader with a DC50 of 12 nM. It is a valuable tool for studying synthetic lethal interactions in cancers with SMARCA4 mutations, such as non-small cell lung cancer. The compound is not FDA-approved and has not completed clinical trials. It is for research use only. The CAS number for the free base is 3033109-92-8. Store as powder at -20degC.
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| Molecular Formula |
C54H67F3N10O7S
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|---|---|
| Molecular Weight |
1057.23
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| Related CAS # |
SMD-3040
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| Appearance |
Off-white to light yellow 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 0.9459 mL | 4.7293 mL | 9.4587 mL | |
| 5 mM | 0.1892 mL | 0.9459 mL | 1.8917 mL | |
| 10 mM | 0.0946 mL | 0.4729 mL | 0.9459 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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