GSK4112, a Small Molecule Chemical Probe for the Cell Biology of the Nuclear Heme Receptor Rev-erbα

A small molecule ligand, GSK4112, was identified as a competitive inhibitor of heme for the orphan nuclear receptor Rev-erbα.

• GSK4112 acts as a Rev-erbα agonist, inhibiting the expression of the circadian target gene bmal1.
• The compound also repressed the expression of gluconeogenic genes in liver cells.
• GSK4112 reduced glucose output in primary hepatocytes.
• The findings suggest that GSK4112 may be a valuable tool for studying the role of Rev-erbα in transcriptional repression and metabolic regulation.
• It could serve as a foundation for developing chemical probes targeting Rev-erbα with in vivo effects.

AI simplified