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. 2021 Mar 12;7(11):eaba1187. doi: 10.1126/sciadv.aba1187

Fig. 1. TAK-418 is a specific inhibitor of LSD1 enzyme activity.

Fig. 1

(A) Chemical structure of TAK-418. (B to D) Effects of 3-day TAK-418 treatment on H3K4me2 (B) and H3K9me2 (C) levels at the Ucp2 gene and Ucp2 mRNA levels (D) in primary cultured rat neurons. N = 3 to 4. One-tailed parametric Williams’ test versus DMSO-treated groups, *P < 0.025, **P < 0.005, and ***P < 0.0005. (E) Immunoprecipitation (IP) analyses of the interaction between LSD1 and GFI1B in TF-1a cells. GFI1B/LSD1 values are obtained from densitometry data of GFI1B bands normalized by LSD1 bands (lane 9 = 100%). IgG, immunoglobulin G; WB, Western blotting. (F) Superimposed structure of formylated FAD (stick model in white) in human recombinant LSD1 generated after TAK-418 treatment and N-terminal GFI1B peptide (PRSFLV, stick model in yellow) in the LSD1 complex. The formyl-FAD adduct is compact in the active site of LSD1 and has minimal impact on the interaction between LSD1 and GFI1B. (G) Dose-dependent change in LSD1 enzyme activity in the rat cortex 2 hours after administration of TAK-418. N = 3 to 6. One-tailed Shirley-Williams test versus vehicle-treated group, **P < 0.005. Data are shown as means + SD.