SR9011 hydrochloride is aREV-ERBα/βagonist withIC₅₀s of 790 nM and 560 nM for REV-ERBα and REV-ERBβ, respectively.

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

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 theBmal1promoter (SR9011 IC₅₀=620 nM). SR9011 suppresses the expression ofBMAL1 mRNA in HepG2 cells in aREV-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/G₁phase and a decrease of cells in S and G₂/M phase suggesting that activation of REV-ERB may be resulting in decreased transition from G₁to S phase and/or from S to G₂/M phase^[2].

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. Theplasminogen activator inhibitor type 1gene (Serpine1) is a REV-ERB target gene and displays dose-dependent suppression of expression in response to SR9011. Thecholesterol 7α-hydroxylase(Cyp7a1) andsterol 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 ofRev-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].

515.50

Solid

C₂₃H₃₂Cl₂N₄O₃S

2070014-94-5

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

DMSO : ≥ 32 mg/mL(62.08 mM)

H₂O :< 0.1 mg/mL (ultrasonic;warming;heat to 60℃)(insoluble)

*"≥" means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。