| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
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| Targets |
IC50: 790 nM (Rev-ErbBα), 560 nM (Rev-ErbBβ)[1]
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| ln Vitro |
In HEK293 cells expressing a chimeric Gal4 DNA Binding Domain (DBD) - REV-ERB ligand binding domain (LBD) α or β and a Gal4-responsive luciferase reporter (REV-ERBα IC50=790 nM, REV-ERBβ IC50=560 nM), SR9011 dose-dependently boosts the REV-ERB-dependent repressor activity. In a cotransfection test with full-length REV-ERBα and a luciferase reporter powered by the Bmal1 promoter, SR9011 (IC50=620 nM) effectively and potently inhibits transcription. SR9011 inhibits the expression of BMAL1 mRNA in HepG2 cells in a manner that is dependent on REV-ERBα/β[1]. In addition, SR9011 inhibits the growth of breast cancer cell lines irrespective of their ER or HER2 status. It seems that SR9011 stops the breast cancer cells' cell cycle before they enter the M phase. Since cyclin A (CCNA2) is a direct target gene of REV-ERB, the cell cycle arrest may be mediated by SR9011's reduction of this cyclin's expression. Increases in G0/G1 phase cells and decreases in S and G2/M phase cells following SR9011 treatment imply that REV-ERB activation may be causing a reduced transition from G1 to S phase and/or from S to G2/M phase[2].
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| ln Vivo |
Since SR9011 exhibits a respectable plasma exposure, the expression of genes sensitive to REV-ERB is investigated in the livers of mice given varying dosages of SR9011 for a period of six days. As a REV-ERB target gene, the plasminogen activator inhibitor type 1 gene (Serpine1) exhibits dose-dependent expression reduction in response to SR9011. It has also been demonstrated that the REV-ERB-responsive genes cholesterol 7α-hydroxylase (Cyp7a1) and sterol response element binding protein (Srepf1) are inhibited dose-dependently with increasing concentrations of SR9011. Following 12 days in D:D circumstances, mice get a single injection of either SR9011 or a vehicle at CT6, which represents the maximal expression of Rev-erbα. There is no change in circadian locomotor activity after vehicle injection. Nevertheless, during the subject dark phase, a single dose of SR9011 causes a decrease of locomotor activity. The resumption of normal activity to the following circadian cycle is consistent with the medications clearing in less than twenty-four hours. The efficacy (ED50=56 mg/kg) of the SR9011-dependent reduction in wheel running behavior in mice kept in permanent darkness is comparable to that of the SR9011-mediated in vivo inhibition of the REV-ERB responsive gene Srebf1 (ED50=67 mg/kg)[1].
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| References |
[1]. Solt LA, et al. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature. 2012 Mar 29;485(7396):62-8.
[2]. Wang Y, et al. Anti-proliferative actions of a synthetic REV-ERBα/β agonist in breast cancer cells. Biochem Pharmacol. 2015 Aug 15;96(4):315-22 |
| Molecular Formula |
C23H32CL2N4O3S
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|---|---|
| Molecular Weight |
515.50
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| CAS # |
2070014-94-5
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| Related CAS # |
SR9011;1379686-29-9
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| SMILES |
ClC1C=CC(=CC=1)CN(CC1=CC=C([N+](=O)[O-])S1)CC1CN(C(NCCCCC)=O)CC1.Cl
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| Solubility (In Vitro) |
DMSO: ≥ 32 mg/mL (62.08 mM)
H2O: < 0.1 mg/mL |
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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 | 1.9399 mL | 9.6993 mL | 19.3986 mL | |
| 5 mM | 0.3880 mL | 1.9399 mL | 3.8797 mL | |
| 10 mM | 0.1940 mL | 0.9699 mL | 1.9399 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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