Figure 1. Imirestat inhibits SCoR2 activity but fails to protect against AKI.

(A-D) IC₅₀ values of four known AKR1B1 inhibitor compounds (imirestat, sorbinil, epalrestat and tolrestat) against purified SCoR2 using DL-glyceraldehyde as substrate (n=3). (E) IC₅₀ value of imirestat to inhibit SCoR2 using SNO-CoA as substrate (n=3). (F) SNO-CoA metabolizing activity of kidneys from imirestat-treated mice (i.p. at the indicated dose) vs vehicle (DMSO)-treated or SCoR2-knockout (SCoR2^−/−) mice (n=3). (G) SNO-CoA-metabolizing activity in AKI-injured kidneys from mice on normal diet (n=5) and imirestat diet-fed mice (for the indicated times) (n=3). (H-I) Serum creatinine and blood urea nitrogen (BUN) levels in serum from mice injected i.p. with imirestat 18h prior to I/R-induced AKI (n=7). (J-K) Serum creatinine and BUN in imirestat diet-fed mice (for the indicated times) subjected to I/R-induced AKI (n=3). (L) IC₅₀ value of imirestat against AKR1B1 using DL-glyceraldehyde as substrate (n=3). (M) IC₅₀ value of imirestat against AKR1B1 using methylglyoxylate as substrate (n=3). All results are presented as mean ± SD. Two-tailed Student’s t-test was used to detect significance. *, p<0.05; **, p<0.01; NS, not significant.