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REV-ERBα is a nuclear hormone receptor with roles in circadian rhythm, adipogenesis, lipid metabolism, and inflammation. It binds porphoryin heme and in response to fluctuations in heme levels in cells it recruits corepressors such as NCoR and HDAC3 to repress the transcription of key genes involved in metabolic and circadian pathways., GSK4112 is a synthetic agonist for REV-ERBα (EC50 = 0.4 μM) that was designed to mimic the action of heme., At 10 μM, GSK4112 can reset the circadian rhythm in a phasic manner by inhibiting expression of the circadian target gene bmal1 and reduce glucose output by 30% in mouse primary hepatocytes by repressing the expression of several gluconeogenic genes. GSK4112 has been used to investigate the function of REV-ERBα in the coordination of circadian rhythm and metabolism in rat ovaries.
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