| SR9011 Usage And Synthesis |
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| Biochem/physiol Actions | SR9011 is a potent nuclear receptor REV-ERB agonist (EC50 of REV-ERBα- and REV-ERBβ-dependent repressor activity = 790 and 560 nM, respectively, by cell-based reporter assay) that stimulates REV-ERB-dependent target genes suppression both in cultures in vitro and in mice in vivo (100 mg/kg i.p., b.i.d.) without activity toward a panel of 46 other nuclear receptors. SR9011 is shown to modulate circadian behavior by suppressing the transcription factors BMAL1 (brain and muscle ARNT-like protein 1) and CLOCK (circadian locomotor output cycles kaput) as well as induce energy expenditure and weight loss by regulating genes involved in lipid and glucose metabolism in mice in vivo with good bioavailabiilty (plasma conc. = 0.53 and 15.3 μM 2 hr post 10 or 100 mg/kg i.p. dosage; brain conc. = 0.24 μM 2 hr post 10 mg/kg i.p.), while its structure analog GSK4112 shows no plasma exposure. |
| Uses | SR 9011 is a synthetic REV-ERBα/β agonist with activity in vivo. It is a lead compound for a new class of cancer drugs associated with the body’s circadian clock. |
| Application | SR9011 has been used as a nuclear receptor subfamily 1 group D member 1 (NR1D1) receptor agonist:
to study its effects on microglial immune-metabolism
to study its effects on insulin secretion from human type 2 diabetes islet cells
to study its effects on thyroid-stimulating hormone β (TSHβ) gene expression |
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