Fig. 1|. CBR-470-series compounds activate NRF2 signaling in vitro and in vivo.

a, Structure of CBR-470-1. b, NRF2 protein levels from IMR32 cells treated with the indicated concentrations of CBR-470-1 for 4 hours (top) or 5 μM CBR-470-1 for the indicated time periods (bottom). Blots are representative of 3 independent experiments. c, GSEA enrichment plot depicting the enrichment of a NRF2 target gene set (“Singh_NFE2L2_Targets” in MSigDB) from IMR32 cells treated for 24 hours with 5 μM CBR-470-1 (n=3, P < 0.0001, nom. p-value in GSEA). d, Heat map representation of the leading-edge subset of the most upregulated NRF2-regulated transcripts upon CBR-470-1 treatment. Data are biologically independent samples. e, Relative Nqo1 and Hmox1 transcript levels 24 hr after indicated P.O. doses of CBR-470-2 (n=6, biologically independent samples). f, Quantification of wounded area by automated image analysis from animals of the indicated treatment groups at study end (day 10). g, Quantification of epidermal thickness from H&E stained sections from the indicated groups at study end. h, Representative images of H&E stained skin sections from animals sacrificed at day 10 of the study. CBR-470-2, 50 mg/kg BID PO; BARD, bardoxolone methyl, 3mg/kg BID PO; UV, 200 mJ/cm²; data are mean and s.e.m., n=8 animals. Statistical analyses are one-way ANOVA with Dunnett’s correction (e-g). Data are mean and s.e.m.