| Targets |
SMARCA2 (also known as BRM), a core ATPase subunit of the SWI/SNF chromatin remodeling complex. SMD-3040 is a PROTAC that simultaneously binds to SMARCA2 and an E3 ubiquitin ligase, leading to ubiquitination and proteasomal degradation of SMARCA2. This degradation disrupts the SWI/SNF complex, which is essential for chromatin remodeling and gene expression. SMARCA2 is a synthetic lethal target in cancers with loss of the related SMARCA4 protein, making SMD-3040 a potential therapeutic strategy for such tumors.
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| ln Vitro |
In vitro, SMD-3040 formate demonstrates potent degradation of SMARCA2 protein. In cell-based assays, it achieves a DC50 of 12 nM, indicating half-maximal degradation at very low concentrations, with a maximum degradation (Dmax) of 91%. It selectively degrades SMARCA2 over other SWI/SNF components. This degradation leads to inhibition of tumor cell proliferation. It exhibits potent antiproliferative activity in cancer cell lines that are dependent on SMARCA2 for survival. It does not affect SMARCA4, the paralog of SMARCA2.
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| ln Vivo |
In vivo, SMD-3040 formate exhibits strong antitumor activity. In mouse xenograft models, administration of SMD-3040 leads to significant tumor growth inhibition. The compound's efficacy is attributed to the degradation of SMARCA2 in tumor tissues, as confirmed by Western blot analysis of harvested tumors. It demonstrates a favorable in vivo profile with potent activity. The specific dosing regimens, routes of administration, and toxicity profiles are not detailed in the available literature.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays are not the primary method for characterizing PROTACs like SMD-3040. Instead, cellular target engagement and degradation assays are used. However, binding affinity to SMARCA2 and the E3 ligase can be measured using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC) in cell-free systems. These assays confirm the binary interactions required for PROTAC activity. The compound is incubated with recombinant SMARCA2 protein or E3 ligase, and binding kinetics are determined.
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| Cell Assay |
In vitro cell-based assays for SMD-3040 are performed in cancer cell lines. Cells are treated with varying concentrations of SMD-3040 for a defined period (e.g., 4-24 hours). SMARCA2 protein levels are measured by Western blot to determine DC50 and Dmax. Cell proliferation is assessed using CellTiter-Glo or MTT assays after longer treatment durations (e.g., 72-120 hours). Selectivity is confirmed by assessing the levels of other proteins, including SMARCA4. Apoptosis is measured by caspase activation or Annexin V staining. These assays establish the compound's potency and selectivity.
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| Animal Protocol |
In vivo animal experiments with SMD-3040 are conducted in mouse xenograft models. Immunocompromised mice are implanted with cancer cell lines sensitive to SMARCA2 degradation. When tumors reach a certain size, animals are treated with SMD-3040 via intraperitoneal or intravenous injection at various doses. Tumor volume and body weight are monitored regularly. At the end of the study, tumors are harvested for Western blot analysis to confirm SMARCA2 degradation. Efficacy is measured as tumor growth inhibition compared to vehicle control.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of SMD-3040 formate are not detailed in the available literature. As a PROTAC, it is a large molecule (MW 989.2 g/mol) with properties that may affect oral bioavailability. It is typically administered parenterally in animal studies. Its solubility, half-life, clearance, and volume of distribution are unknown. The formate salt form is used to improve solubility and stability. PK studies would be required to characterize its absorption, distribution, metabolism, and excretion for drug development purposes.
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| Toxicity/Toxicokinetics |
Toxicological data for SMD-3040 formate are not detailed in the available literature. It is a research compound not intended for human use. No LD50 values or repeated-dose toxicity studies have been reported. Standard safety pharmacology studies have not been performed. As with all research chemicals, appropriate safety precautions should be taken when handling. Its specific toxicological profile has not been established.
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| References | |
| Additional Infomation |
SMD-3040 formate is a potent and selective SMARCA2 PROTAC degrader with a DC50 of 12 nM and Dmax of 91%. It exhibits strong in vivo antitumor activity. Its molecular formula is C53H68N10O7S, and its molecular weight is 989.2 g/mol. It is a promising candidate for cancer research involving epigenetic regulation and synthetic lethality. It is available for research use only.
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| Molecular Formula |
C53H68N10O7S
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| Molecular Weight |
989.23
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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) |
DMSO :≥ 100 mg/mL (~101.09 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 | 1.0109 mL | 5.0544 mL | 10.1089 mL | |
| 5 mM | 0.2022 mL | 1.0109 mL | 2.0218 mL | |
| 10 mM | 0.1011 mL | 0.5054 mL | 1.0109 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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