REV-ERBα and REV-ERBβ nuclear receptors are transcriptional repressors that coordinate circadian rhythm and metabolic pathways in a heme-dependent manner. SR9009 is a REV-ERB agonist that increases the constitutive repression of genes regulated by REV-ERBα and REV-ERBβ with IC50 values of 670 and 800 nM, respectively. 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. The circadian pattern of expression of an array of metabolic genes in the liver, skeletal muscle and adipose tissue was also shown to be altered in mice exposed to SR9009, resulting in increased energy expenditure. Diet-induced obese mice treated with 100 mg/kg SR9009 (i.p. two times a day for 30 days) have been reported to display decreased fat mass and markedly improved dyslipidemia and hyperglycemia.
