Nrf2 agonist C5 is a novel chalcone-derived covalent Keap1 binder and Nrf2 agonist, strongly blocks Keap1-Nrf2 interaction and enhances Nrf2 stability.
C5 (0.5 μM) showed more potent Nrf2 agonist effects than SFN (10 μM) in HK-2 cells, a known Nrf2 agonist.
C5 could enhance Nrf2 stability and facilitated its nuclear translocation.
C5 (0.5-2 uM) significantly upregulated the transcriptional levels of the target genes of Nrf2, including HO-1, NQO1, GCLC and GCLM in HK-2 cells.
C5 activates Keap1/Nrf2 signaling via covalent modifying these two key cysteines of Keap1 (Cys288 and Cys319), thereby enhancing Nrf2 stability, promoting Nrf2 nuclear translocation and then activating the Keap1-Nrf2 signaling.
C5 ameliorates CDDP-induced kidney injury in HK-2 cells, C5 alleviates CDDP-induced mitochondrial damage.
C5 (5, 10, and 20 mg/kg/d) significantly ameliorates inflammatory injury in CIKI mice, dose-dependently attenuated renal inflammation, reducing pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in kidney tissues.