Identification of SR8278, a Synthetic Antagonist of the Nuclear Heme Receptor REV-ERB

The first REV-ERB antagonist, SR8278, was identified as a chemical tool for exploring REV-ERB function.

• SR8278 blocks the action of the synthetic agonist GSK4112 in enhancing REV-ERBα-dependent gene repression.
• GSK4112 suppresses the expression of target genes related to gluconeogenesis, while SR8278 stimulates their expression.
• SR8278's structure is similar to GSK4112, suggesting a distinct mechanism of action as an antagonist.
• The findings may facilitate the development of REV-ERB antagonists that could help investigate circadian and metabolic processes.

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