SR9009 (Synonyms: REV-ERB Agonist II) |
Catalog No.GC12035
One-Click Copy Product Info
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SR9009 is a potent REV-ERBα/β agonist with EC50 values of 0.67µM and 0.8μM for REV-ERBα and REV-ERBβ, respectively.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1379686-30-2
Sample solution is provided at 25 µL, 10mM.
SR9009 is a potent REV-ERBα/β agonist with EC50 values of 0.67µM and 0.8μM for REV-ERBα and REV-ERBβ, respectively[1]. SR9009 suppresses the senescence-associated secretory phenotype (SASP) and DNA damage response (DDR) activation through the activation of the NRF2 pathway, thereby decreasing the ROS level by regulating the expression of antioxidant enzymes[2]. SR9009 has been widely used to inhibit the activation of the inflammatory responses and to prevent the production of IL-1β[3].
In vitro, SR9009 treatment for 24h significantly inhibited the activity of the HIV-1 long terminal repeat (LTR) promoter in TZM-bl cells, with an IC50 value of 30.6µM[4]. SR9009 treatment for 1 hour significantly inhibited the expression level of Nlrp3 mRNA in Raw 264.7 cells, with an IC50 value of 4.94µM[5]. After 48-hour treatment with SR9009, the viability of U266 and RPMI8226 cells was significantly decreased, with IC50 values of 22.10µM and 29.35µM, respectively[6]. Treatment with 10µM SR9009 for 2 days induced the death of mouse embryonic stem cells (mESCs), promoting mitochondrial stress and altering mitochondrial function[7].
In vivo, SR9009 treatment via intraperitoneal injection at a dose of 100mg/kg/day for 30 days alleviated liver damage, improved liver fibrosis, and reduced the body weight in the non-alcoholic fatty liver disease (NAFLD) mouse model[8]. Intraperitoneal injection of SR9009 at a dose of 50mg/kg/day for 3 consecutive days improved acute neurological deficits, reduced infarct volume, and enhanced motor function in a mouse model of cerebral ischemia[9].
References:
[1] Solt L A, Wang Y, Banerjee S, et al. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists[J]. Nature, 2012, 485(7396): 62-68.
[2] Gao L B, Wang Y H, Liu Z H, et al. Identification of a small molecule SR9009 that activates NRF2 to counteract cellular senescence[J]. Aging Cell, 2021, 20(10): e13483.
[3] Hong H, Cheung Y M, Cao X, et al. REV-ERBα agonist SR9009 suppresses IL-1β production in macrophages through BMAL1-dependent inhibition of inflammasome[J]. Biochemical pharmacology, 2021, 192: 114701.
[4] Borrmann H, Davies R, Dickinson M, et al. Pharmacological activation of the circadian component REV-ERB inhibits HIV-1 replication[J]. Scientific reports, 2020, 10(1): 13271.
[5] Wang S, Lin Y, Yuan X, et al. REV-ERBα integrates colon clock with experimental colitis through regulation of NF-κB/NLRP3 axis[J]. Nature communications, 2018, 9(1): 4246.
[6] Wang R, Liu S L, Guo Q Q, et al. Circadian clock REV-ERBs agonist SR9009 induces synergistic antitumor activity in multiple myeloma by suppressing glucose-regulated protein 78-Dependent autophagy and lipogenesis[J]. World Journal of Oncology, 2023, 14(6): 464.
[7] Dierickx P, Emmett M J, Jiang C, et al. SR9009 has REV-ERB–independent effects on cell proliferation and metabolism[J]. Proceedings of the National Academy of Sciences, 2019, 116(25): 12147-12152.
[8] Griffett K, Bedia-Diaz G, Elgendy B, et al. REV-ERB agonism improves liver pathology in a mouse model of NASH[J]. PloS one, 2020, 15(10): e0236000.
[9] Sheng M, Chen X, Yu Y, et al. Rev-erbα agonist SR9009 protects against cerebral ischemic injury through mechanisms involving Nrf2 pathway[J]. Frontiers in Pharmacology, 2023, 14: 1102567.
| Cell experiment [1]: | |
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Cell lines |
U266 cells |
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Preparation Method |
U266 cells were cultured in RPMI-1640 medium, supplemented with 10% fetal bovine serum (FBS), 100U/ml penicillin, and 100mg/ml streptomycin at 37°C in an incubator with 5% CO2. Cells were seeded in a 96-well plate at a density of 1×104 cells/well for 24h, with three replicates for each treatment. Cells were treated with SR9009 at a range of concentrations (0, 5, 10, 20, 40, and 60μM). After 48h of treatment, the cell viability was determined. |
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Reaction Conditions |
0, 5, 10, 20, 40, and 60μM; 48h |
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Applications |
SR9009 treatment inhibited the cell viability of U266 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
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Animal models |
Male B6 V-Lepob/J (ob/ob) mice |
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Preparation Method |
Male B6 V-Lepob/J (ob/ob) mice (6 weeks old) were maintained in a controlled environment at 21±1°C and 60% relative humidity under a 12h light/dark cycle, and were given free access to the NASH diet. SR9009 was formulated as 100mg/kg at 10mg/ml in 5% DMSO, 15% Cremophore EL, 80% PBS. Both vehicle (5% DMSO, 15% CremophoreEL, 80% PBS) and SR9009 were filter sterilized prior to dosing. Mice were given once daily i.p. injections for 30 days. Livers of mice were collected for analysis. |
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Dosage form |
100mg/kg/day; 30 days; i.p. |
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Applications |
SR9009 treatment significantly reduced hepatic inflammation and suppressed liver fibrosis in mice with the NASH diet. |
References: [1] Wang R, Liu S L, Guo Q Q, et al. Circadian clock REV-ERBs agonist SR9009 induces synergistic antitumor activity in multiple myeloma by suppressing glucose-regulated protein 78-Dependent autophagy and lipogenesis[J]. World Journal of Oncology, 2023, 14(6): 464. [2] Griffett K, Bedia-Diaz G, Elgendy B, et al. REV-ERB agonism improves liver pathology in a mouse model of NASH[J]. PloS one, 2020, 15(10): e0236000. | |
| Cas No. | 1379686-30-2 | SDF | |
| Synonyms | REV-ERB Agonist II | ||
| Chemical Name | ethyl 3-(((4-chlorobenzyl)((5-nitrothiophen-2-yl)methyl)amino)methyl)pyrrolidine-1-carboxylate | ||
| Canonical SMILES | CCOC(N1CCC(C1)CN(CC(S2)=CC=C2[N+]([O-])=O)CC3=CC=C(Cl)C=C3)=O | ||
| Formula | C20H24ClN3O4S | M.Wt | 437.94 |
| Solubility | ≥ 43.8mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2834 mL | 11.4171 mL | 22.8342 mL |
| 5 mM | 456.7 μL | 2.2834 mL | 4.5668 mL |
| 10 mM | 228.3 μL | 1.1417 mL | 2.2834 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 36 reference(s) in Google Scholar.)