| Size | Price | |
|---|---|---|
| 100mg | ||
| 250mg | ||
| 500mg | ||
| Other Sizes |
| Targets |
Kd: 93 nM (SMARCA2), 65 nM (SMARCA4); DC50 for SMARCA2: 39 pM (in SW1573 cells)[1].
|
|---|---|
| ln Vitro |
A947 has a 93 nM and 65 nM Kd value for binding affinity to the SMARCA2 and SMARCA4 bromodomains, respectively[1]. With a DC50 of 39 pM, A947 has the ability to potently degrade SMARCA2 in SW1573 cells[1]. SMARCA2/4 is ubiquitinated and degraded by A947 (100 nM, 500 nM)[1]. A947 (0-500 nM) can stop SMARCA4-mutant NSCLC cells from proliferating[1].
|
| ln Vivo |
In SMARCA4-mutant NSCLC xenograft models, A947 (iv; 40 mg/kg; single-dose, 2 week or every other week, 30 days) has demonstrated activity in vivo[1].
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: SW1573 cells Tested Concentrations: 0-10 nM Incubation Duration: 18 h Experimental Results: Degraded SMARCA2 with amaximal degradation of 96% in 10 nM. Cell Viability Assay[1] Cell Types: NCI-H1944 cells Tested Concentrations: 0-500 nM Incubation Duration: 7 days Experimental Results: demonstrated the dose-dependent inhibition of growth. Cell Cycle Analysis[1] Cell Types: HCC2302, NCI-H1793, RERF-LC-AI, NCI-H1944, Calu-6, NCI-H460, A427 cells Tested Concentrations: 0-500 nM Incubation Duration: 48 h Experimental Results: demonstrated G1 arrest in SMARCA4mut models. Apoptosis Analysis[1] Cell Types: NCI-H1944, NCI-H838 cells Tested Concentrations: 100 nM Incubation Duration: 50 h Experimental Results: Induced cells toward apoptotic cell death. |
| Animal Protocol |
Animal/Disease Models: SMARCA4-mutant NSCLC xenograft models
Doses: 40mg/kg Route of Administration: intravenous (iv), single-dose, 2 week; intravenous (iv), every other week, 30 days Experimental Results: Rapidly diminished the tumor SMARCA2 protein levels and Dramatically diminished the tumor growth. |
| References |
[1]. Jennifer Cantley, et al. Selective PROTAC-mediated degradation of SMARCA2 is efficacious in SMARCA4 mutant cancers. Nat Commun. 2022 Nov 10;13(1):6814.
|
| Molecular Formula |
C61H76N12O7S
|
|---|---|
| Molecular Weight |
1121.40
|
| CAS # |
2378056-80-3
|
| 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)
|
| 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 | 0.8917 mL | 4.4587 mL | 8.9174 mL | |
| 5 mM | 0.1783 mL | 0.8917 mL | 1.7835 mL | |
| 10 mM | 0.0892 mL | 0.4459 mL | 0.8917 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
