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CAS 1379686-29-9 SR9011
SR9011 is a potent and specific synthetic REV-ERB agonist that binds to REV ERB α with an EC50 ~790 nM and REV-ERB-β with EC50 ~560 nM. It also has good in vivo plasma/brain exposure. The nuclear receptors REV-ERB-α and REV-ERB-β play an integral role in regulating the expression of core clock proteins, driving rhythms in activity and metabolism. Administration of SR9011 alters circadian behavior and the circadian pattern of core clock gene expression in the hypothalami of mice.
The circadian expression pattern of an array of metabolic genes in the liver, skeletal muscle and adipose tissue was also altered, resulting in increased energy expenditure. Treatment of diet induced obese mice with SR9011 decreased obesity by reducing fat mass and markedly improved dyslipidaemia and hyperglycaemia. These results indicate that synthetic REV-ERB ligands that pharmacologically target the circadian rhythm may be beneficial in the treatment of sleep disorders as well as metabolic diseases.
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