SR-9009

Modify Date: 2024-01-02 22:13:11

SR-9009 Structure
SR-9009 structure
Common Name SR-9009
CAS Number 1379686-30-2 Molecular Weight 437.94000
Density 1.3±0.1 g/cm3 Boiling Point 547.2±45.0 °C at 760 mmHg
Molecular Formula C20H24ClN3O4S Melting Point N/A
MSDS N/A Flash Point 284.7±28.7 °C

 Use of SR-9009


SR9009 is a REV-ERBα/β agonist with IC50s of 670 nM and 800 nM for REV-ERBα and REV-ERBβ, respectively.

 Names

Name Ethyl 3-({(4-chlorobenzyl)[(5-nitro-2-thienyl)methyl]amino}methyl)-1-pyrrolidinecarboxylate
Synonym More Synonyms

 SR-9009 Biological Activity

Description SR9009 is a REV-ERBα/β agonist with IC50s of 670 nM and 800 nM for REV-ERBα and REV-ERBβ, respectively.
Related Catalog
Target

IC50: 670 nM (Rev-ErbBα), 800 nM (Rev-ErbBβ)[1]

In Vitro SR9009 dose-dependently increases the REV-ERB-dependent repressor activity assessed 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 (SR9009: REV-ERBα IC50=670 nM, REV-ERBβ IC50=800 nM). SR9009 potently and efficaciously suppresses transcription in a cotransfection assay using full-length REV-ERBα along with a luciferase reporter driven by the Bmal1 promoter (IC50=710 nM). SR9009 suppresses the expression of BMAL1 mRNA in HepG2 cells in a REV-ERBα/β-dependent manner. Direct binding of the SR9009 to REV-ERBα is also confirmed using circular dichrosim analysis (Kd=800 nM)[1].
In Vivo While the stress of handling and twice-daily injections caused weight loss in vehicle-treated controls, weight loss of SR9009-treated animals is 60% greater. SR9009 (100 mg/kg ,i.p.) treated mice exhibit a more severe reduction in adiposity. Plasma non-esterified fatty acids (NEFA) are also reduced (23%) along with plasma glucose (19%) in the SR9009 treated animals. In the white adipose tissue (WAT) , SR9009 treatment results in a decrease in expression of genes encoding enzymes involved in triglyceride (TG) synthesis as is also observed in lean mice[1].
Cell Assay HEK293 cells are grown in 96-well plates (1×106/well) and are transiently transfected using Lipofectamine. Cells are transfected with a total of 200 ng of DNA per well consisting of the pGL4 mIL-17 firefly luciferase reporter construct, the pGL4 mIL-17 + CNS-5 firefly luciferase reporter construct, or the pGL4 mIL-17 2kB RORE mutant (100 ng/well) , an actin promoter Renilla reniformis luciferase reporter (50 ng/well), and either control vector alone or the test DNA (full-length RORα or full-length RORγ at 50 ng/well). All 48 human nuclear receptors are represented in the specificity assay and SR9009 is tested at a concentration of 20 μM. The format of the assay is a cotransfection assay with Gal4 DNA binding domain-nuclear receptor fusions in HEK293 cells[1].
Animal Admin Mice[1] For circadian gene expression experiments male C57BL6 mice (8-10 weeks of age) are either maintained on a L:D (12h:12h) cycle or on constant darkness. At circadian time (CT) 0 animals are administered a single dose of 100 mg/kg SR9009 or SR9011 (i.p.) and groups of animals (n=6) are sacrificed at CT0, CT6, CT12 and CT18. Gene expression is determined by real time QPCR.
References

[1]. Solt LA, et al. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature. 2012 Mar 29;485(7396):62-68.

 Chemical & Physical Properties

Density 1.3±0.1 g/cm3
Boiling Point 547.2±45.0 °C at 760 mmHg
Molecular Formula C20H24ClN3O4S
Molecular Weight 437.94000
Flash Point 284.7±28.7 °C
Exact Mass 437.11800
PSA 106.84000
LogP 4.17
Vapour Pressure 0.0±1.5 mmHg at 25°C
Index of Refraction 1.608
Storage condition 2-8℃

 Synonyms

1-Pyrrolidinecarboxylic acid, 3-[[[(4-chlorophenyl)methyl][(5-nitro-2-thienyl)methyl]amino]methyl]-, ethyl ester
Ethyl 3-({(4-chlorobenzyl)[(5-nitro-2-thienyl)methyl]amino}methyl)-1-pyrrolidinecarboxylate
SR9009
STENABOLIC
SR 9009
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