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. 2023 Sep 25;14:5971. doi: 10.1038/s41467-023-41570-6

Fig. 4. ALDH2 (Acetaldehyde Dehydrogenase 2) activator AD-9308 enhanced ALDH2 enzymatic activities.

Fig. 4

a Prodrug AD-9308 is converted to AD-5591 by esterase hydrolysis in vivo. b AD-5591 (100 μM) or alda-1 (100 μM) significantly increases the enzymatic activity of recombinant WT and mutant human ALDH2 proteins (n = 3 per group in duplicates, left panel: one-way analysis of variance (ANOVA) P < 0.0001, Tukey’s post hoc test: column 1 vs. 2: P = 0.04, column 1 vs. 3: P < 0.001, and column 2 vs. 3. P < 0.001, right panel: one-way ANOVA P < 0.0001, Tukey’s post hoc test: column 1 vs. 2: P = 0.0056, column 1 vs. 3: P = 0.0006, and column 2 vs. 3. P < 0.001). c Ribbon diagram showing the binding pocket of AD-5591 within human WT ALDH2. d LigPlot (Ligand-Protein Interaction Diagrams) showing the bonds between AD-5591 and human WT ALDH2. e Regional ribbon diagram showing the binding of AD-5591 and NAD+ with WT ALDH2. Figure (b) was analyzed by one-way ANOVA with Tukey’s post-hoc tests. All data are presented as mean and standard error (S.E.M.). The n values represent biological repeats and the number of technical repeats were expressed as duplicates or triplicates. The asterisks indicate two-sided *P < 0.05, **P < 0.01, ***P < 0.001.