SR 8278

REV-ERBα is a nuclear receptor and transcription repressor that coordinates circadian rhythm and metabolic pathways in a heme-dependent manner.[1],[2] SR8278 is an antagonist of REV-ERBα (EC50 = 0.47 µM), blocking activation of the receptor by the synthetic agonist GSK 4112.[2] Moreover, SR8278 stimulates the expression of two REV-ERBα target genes involved in the regulation of glucose production, glucose 6-phosphatase and phosphoenolpyruvate carboxykinase, in liver cells.2 SR8278 has been used, with GSK 4112, to elucidate the role of REV-ERBα in regulating glucagon secretion in pancreatic alpha cells.[3]

Reference:
[1]. Duez, H., and Staels, B. Rev-erb-α: An integrator of circadian rhythms and metabolism. Journal of Applied Physiology 107(6), 1972-1980 (2009).
[2]. Kojetin, D., Wang, Y., Kameneck, T.M., et al. Identification of SR8278, a synthetic antagonist of the nuclear heme receptor REV-ERB. ACS Chemical Biology 6(2), 131-134 (2011).
[3]. Vieira, E., Marroquí, L., Figueroa, A.L., et al. Involvement of the clock gene Rev-erb alpha in the regulation of glucagon secretion in pancreatic alpha-cells. PLoS One 8(7), 1-15 (2013).