S217879 (S 217879) is a highly potent and selective NRF2 activator, binds to KEAP1 Kelch domain (SPR Kd=4.15 nM), disrupts the KEAP1-NRF2 interaction leading to robust NRF2 pathway activation.
S217879 displays high selectivity for KEAP1 binding in a broad selectivity panel comprising 110 targets at 10 uM.
S217879 significantly activated a reporter gene driven by an ARE in HepG2 cells in a concentration-dependent manner with an EC50 of 18 nM, reduced H2O2-stimulated ROS production in HepG2 cells.|
In hPBMCs, S217879 treatment for 6 h resulted in a concentration-dependent increase in Nqo1 gene expression with an EC50 of 16 nM.
Pretreatment for 4 h with S217879 led to a significant and concentration-dependent inhibition of LPS-induced cytokine release as measured by IL1β, MCP-1 and IL6 MagPix multiplex assays.
S217879 (30 mg/kg, PO, QD) reduced NASH progression in MCDD mice in a dose-dependent manner, reduced NASH progression and liver fibrosis in DIO NASH mice model.