SR9009

• CAT Number: I001464
• CAS Number: 1379686-30-2
• Molecular Formula: C20H24ClN3O4S
• Molecular Weight: 437.9
• Purity: ≥95%
• Target: Nuclear Receptors
• Solubility: DMSO: ≥ 30 mg/mL
• Storage: Store at -20°C
• IC50: 670 nM (Rev-ErbBα), 800 nM (Rev-ErbBβ)
• InChI: InChI=1S/C20H24ClN3O4S/c1-2-28-20(25)23-10-9-16(13-23)12-22(11-15-3-5-17(21)6-4-15)14-18-7-8-19(29-18)24(26)27/h3-8,16H,2,9-14H2,1H3
• InChIKey: MMJJNHOIVCGAAP-UHFFFAOYSA-N
• SMILES: ClC(C=C1)=CC=C1CN(CC2CCN(C(OCC)=O)C2)CC3=CC=C([N+]([O-])=O)S3

SR9009(cas 1379686-30-2) is an agonist of  REV-ERB with IC50 = 670 nM for REV-ERBα and IC50 = 800 nM for REV-ERBβ. REV-ERBα and REV-ERBβ nuclear receptors are transcriptional repressors that coordinate circadian rhythm and metabolic pathways in a heme-dependent manner.  Through activation of REV-ERB, SR9009 has been shown to decrease circadian locomotor activity during the dark phase and to alter the expression pattern of core clock genes in the hypothalami of mice.

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 potently and efficaciously suppresses transcription in a cotransfection assay using full-length REV-ERBα along with a luciferase reporter driven by the Bmal1 promoter (SR9009 IC50=710 nM). SR9009 suppresses the expression of BMAL1 mRNA in HepG2 cells in a REV-ERBα/β-dependent manner.
in vivo: SR9009 are synthetic REV-ERB agonists with activity. SR9009 also inhibits the activity of the SCN clock, with reversible inhibition of circadian oscillations in SCN explants cultured from the Per2:luc reporter mouse.

Reference

1. Int J Mol Sci. 2016 Oct 3;17(10). pii: E1676.

In Vitro Metabolic Studies of REV-ERB Agonists SR9009 and SR9011.

Geldof L(1), Deventer K(2), Roels K(3), Tudela E(4), Van Eeno P(5).

Author information:
(1)Department of Clinical Chemistry, Microbiology and Immunology, Doping Control
Laboratory (DoCoLab), Ghent University, Technologiepark 30 B, B-9052 Zwijnaarde,
9000 Ghent, Belgium. .
(2)Department of Clinical Chemistry, Microbiology and Immunology, Doping Control
Laboratory (DoCoLab), Ghent University, Technologiepark 30 B, B-9052 Zwijnaarde,
9000 Ghent, Belgium. .
(3)Department of Clinical Chemistry, Microbiology and Immunology, Doping Control
Laboratory (DoCoLab), Ghent University, Technologiepark 30 B, B-9052 Zwijnaarde,
9000 Ghent, Belgium. .
(4)Department of Clinical Chemistry, Microbiology and Immunology, Doping Control
Laboratory (DoCoLab), Ghent University, Technologiepark 30 B, B-9052 Zwijnaarde,
9000 Ghent, Belgium. .
(5)Department of Clinical Chemistry, Microbiology and Immunology, Doping Control
Laboratory (DoCoLab), Ghent University, Technologiepark 30 B, B-9052 Zwijnaarde,
9000 Ghent, Belgium.

SR9009 and SR9011 are attractive as performance-enhancing substances due to their
REV-ERB agonist effects and thus circadian rhythm modulation activity. Although
no pharmaceutical preparations are available yet, illicit use of SR9009 and
SR9011 for doping purposes can be anticipated, especially since SR9009 is
marketed in illicit products. Therefore, the aim was to identify potential
diagnostic metabolites via in vitro metabolic studies to ensure effective
(doping) control. The presence of SR9009 could be demonstrated in a black market
product purchased over the Internet. Via human liver microsomal metabolic assays,
eight metabolites were detected for SR9009 and fourteen metabolites for SR9011 by
liquid chromatography-high resolution mass spectrometry (LC-HRMS). Structure
elucidation was performed for all metabolites by LC-HRMS product ion scans in
both positive and negative ionization mode. Retrospective data analysis was
applied to 1511 doping control samples previously analyzed by a full-scan LC-HRMS
screening method to verify the presence of SR9009, SR9011 and their metabolites.
So far, the presence of neither the parent compound nor the metabolites could be
detected in routine urine samples. However, to further discourage use of these
potentially harmful compounds, incorporation of SR9009 and SR9011 into screening
methods is highly recommended.