GSK4112 | Rev-Erbα agonist

GSK4112 (1216744-19-2) is a selective Rev-Erbα agonist (EC₅₀=250 nM).^1,2 It induces circadian clock phase shifts in isolated primary lung fibroblasts as well as in lung slices (10 µM).¹ GSK4112 showed an inhibitory effect on the amplitude of circadian oscillations and caused an arrhythmic expression of canonical clock genes.³ In murine RAW264 macrophages it suppressed inflammatory functions via repressing Ccl2 expression.⁴  It protected RANKL-induced bone loss via inhibition of osteoclast differentiation in vivo.⁵

References/Citations:

1. Meng et al. (2008), Ligand modulation of REV-ERBalpha function resets the peripheral circadian clock in a phasic manner; J. Cell. Science, 121 3629
2. Grant et al. (2010), GSK4112, a small molecule chemical probe for the cell biology of the nuclear heme receptor Rev-erbα; ACS Chem. Biol., 5 925
3. Chen et al. (2015), Integration of the nuclear receptor REV-ERBα linked with circadian oscillators in the expressions of Alas1, Ppargc1a, and Il6 genes in rat granulosa cells; Chronobiol. Int., 32 739
4. Sato et al. (2014), A circadian clock gene, Rev-erbα, modulates the inflammatory function of macrophages through the negative regulation of Ccl2 expression; J. Immunol., 192 407
5. Kim et al. (2020), Rev-erbα Negatively Regulates Osteoclast and Osteoblast Differentiation through p38 MAPK Signaling Pathway; Mol. Cells, 43 34