1. Autophagy
  2. Autophagy

SR9011 hydrochloride 

Cat. No.: HY-16988A
Handling Instructions

SR9011 hydrochloride is a REV-ERBα/β agonist with IC50s of 790 nM and 560 nM for REV-ERBα and REV-ERBβ, respectively.

For research use only. We do not sell to patients.
SR9011 hydrochloride Chemical Structure

SR9011 hydrochloride Chemical Structure

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 272 In-stock
2 mg USD 120 In-stock
5 mg USD 240 In-stock
10 mg USD 420 In-stock
50 mg USD 1800 In-stock
100 mg USD 2520 In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

Customer Review

Other Forms of SR9011 hydrochloride:

  • Biological Activity

  • Protocol

  • Technical Information

  • References

Description

SR9011 hydrochloride is a REV-ERBα/β agonist with IC50s of 790 nM and 560 nM for REV-ERBα and REV-ERBβ, respectively.

IC50 & Target

IC50: 790 nM (Rev-ErbBα), 560 nM (Rev-ErbBβ)[1]

In Vitro

SR9011 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 (REV-ERBα IC50=790 nM, REV-ERBβ IC50=560 nM). SR9011 potently and efficaciously suppresses transcription in a cotransfection assay using full-length REV-ERBα along with a luciferase reporter driven by the Bmal1 promoter (SR9011 IC50=620 nM). SR9011 suppresses the expression ofBMAL1 mRNA in HepG2 cells in a REV-ERBα/β-dependent manner[1] SR9011 suppresses proliferation of the breast cancer cell lines regardless of their ER or HER2 status. SR9011 appears to pause the cell cycle of the breast cancer cells prior to M phase. Cyclin A (CCNA2) is identified as a direct target gene of REV-ERB suggesting that suppression of expression of this cyclin by SR9011 may mediate the cell cycle arrest. Treatment with SR9011 results in an increase in cells in the G0/G1 phase and a decrease of cells in S and G2/M phase suggesting that activation of REV-ERB may be resulting in decreased transition from G1 to S phase and/or from S to G2/M phase[2].

In Vivo

SR9011 displays reasonable plasma exposure, thus, the expression of REV-ERB responsive genes is examined in the liver of mice treated with various doses of SR9011 for 6-days. The plasminogen activator inhibitor type 1 gene (Serpine1) is a REV-ERB target gene and displays dose-dependent suppression of expression in response to SR9011. The cholesterol 7α-hydroxylase (Cyp7a1) and sterol response element binding protein (Srepf1) genes have also been shown to be responsive to REV-ERB and are dose-dependently suppressed with increasing amounts of SR9011. After 12 days in D:D conditions mice are injected with a single dose of SR9011 or vehicle at CT6 (peak expression of Rev-erbα). Vehicle injection causes no disruption in circadian locomotor activity. However, administration of a single dose of SR9011 results in loss of locomotor activity during the subject dark phase. Normal activity returns the next circadian cycle, consistent with clearance of the drugs in less than 24h. The SR9011-dependent decrease in wheel running behavior in the mice under constant darkness conditions is dose-dependent and that the potency (ED50=56 mg/kg) is similar to the potency of SR9011-mediated suppression of a REV-ERB responsive gene, Srebf1 , in vivo (ED50=67mg/kg)[1].

References
Preparing Stock Solutions
Concentration Volume Mass 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
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[2]

SR9011 is dissolved in DMSO and stored, and then diluted with appropriate medium before use[2].

MCF10A, MDA-MB-231, MCF-7, MDA-MB-361, SKBR3, BT474 cells are plated in 6-well plates one day before treatment. The MTT cell proliferation assays are performed. Briefly, 3×103 to 5 × 103 cells per well are plated in 96-well plates. Twenty-four hours later, cells are treated with SR9011 (0, 2, 4, 6, 8 and 10 μM) or DMSO. Seventy-two hours after treatment, the cells are labeled with 1.2 mM MTT and incubated for 4 hours. DMSO is then added and readings are taken on a plate reader at 540 nm[2].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

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 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.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

515.5

Formula

C₂₃H₃₂Cl₂N₄O₃S

Storage
Pure form -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 32 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Inquiry Online

Your information is safe with us. * Required Fields.

Product name

 

Salutation

Applicant name *

 

Email address *

Phone number *

 

Organization name *

Country *

 

Requested quantity *

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
SR9011 hydrochloride
Cat. No.:
HY-16988A
Quantity: