Description |
SR-9009 is an agonist at nuclear receptor Rev-ErbA. Greatly diminishes VILI-induced lung edema, inflammatory cell infiltration and TNFα production in a rat lung injury model. SR-9009 suppresses atherosclerosis in a mouse model. Specifically lethal to cancer cells and oncogene-induced senescent cells with no effect on the viability of normal cells or tissues. Disrupts pain associated with osteoarthritis by reducing BMAL1 expression in bmal1f/fNav1.8CreERT mice. |
Uses |
SR 9009 is a synthetic REV-ERB agonist that regulates circadian behavior and metabolism; has potential use in the treatment of sleep disorders and metabolic diseases. It is a lead compound for a new class of cancer drugs associated with the body’s circadian clock. |
Pharmaceutical Applications |
SR9009 is a research drug that was developed by professor Thomas Burris of the Scripps Research Institute as an agonist of Rev-ErbA (i.e., increases the constitutive repression of genes regulated by Rev-ErbA) with a half-maximum inhibitory concentration (IC50) = 670 nM for Rev-ErbAα and IC50 = 800 nM for Rev-ErbAβ. |
Biological Activity |
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. |