Is SR9009 good for the liver?

SR9009 is the synthetic ligand for Rev-erbs, designed based on the chemical structure of GSK4112. Rev-erbα activation by SR9009, the synthetic ligand for Rev-erbs, inhibited LPS-stimulated transcription of inflammatory factors IL-1β, IL-6, MMP-9, and Ccl2 in astrocytes. SR9009 significantly attenuated hepatic damage and inflammatory responses. This compound administration in mice at 1 day after myocardial ischemic-reperfusion prevents the heart failure by targeting the cardiac inflammasome.

This compound is effective in suppressing clinical markers of liver damage, circulating lipids, hepatic fibrosis, and markers of inflammation. In addition, Pharmacological activation of REV-ERBα by SR9009 alleviated hepatic steatosis, insulin resistance, liver inflammation, and fibrosis in CL diet-induced NASH mice. These effects were accompanied by improved gut barrier function and altered microbial composition and function in NASH mice, and the effect tended to be stronger when SR9009 was injected at ZT0. Moreover, SR9009 treatment at different time points resulted in a marked difference in the composition of the microbiota, with a stronger effect on the enrichment of beneficial bacteria and the diminishment of harmful bacteria when SR9009 was administrated at ZT0.

References

[1] Mingyue Sheng. “Rev-erbα agonist SR9009 protects against cerebral ischemic injury through mechanisms involving Nrf2 pathway.” Frontiers in Pharmacology 14 (2023): 1102567.

[2] Yinhua Ni. “Time-dependent effect of REV-ERBα agonist SR9009 on nonalcoholic steatohepatitis and gut microbiota in mice.” Chronobiology International 40 6 (2023): 769–782.

[3] Kristine Griffett. “REV-ERB agonism improves liver pathology in a mouse model of NASH.” PLoS ONE (2020): e0236000.