LSD1/HDAC-IN-3 is an inhibitor targeting class I HDACs and LSD1. It effectively inhibits HDAC1, HDAC2, HDAC3, and LSD1 with IC50 values of 1702 nM, 842 nM, 358 nM, and 1074 nM, respectively. Demonstrating antioxidant properties, it increases acetylation and methylation of histone H3 in H2O2-treated ARPE-19 and 661W retinal cells. In the rd10 mouse model of retinitis pigmentosa, LSD1/HDAC-IN-3 enhances photoreceptor survival. It is applicable for studying hereditary retinal diseases such as retinitis pigmentosa (RP).

HDAC1:1702 nM

LSD1/HDAC-IN-3 (Compound (±)-3d) exhibits inhibitory activity against class I HDACs and LSD1 with IC50 values of 1702 nM for HDAC1, 842 nM for HDAC2, 358 nM for HDAC3, and 1074 nM for LSD1, while showing no significant inhibition for HDAC6, HDAC8, or HDAC10. At concentrations of 10-30 μM over 24 hours, LSD1/HDAC-IN-3 significantly protects ARPE-19 and 661W cells from H2O2-induced oxidative damage, as evidenced by an increase in cell viability. Additionally, treatment with 10 μM of LSD1/HDAC-IN-3 for the same duration leads to partial increases in acetylation of histone H3 (ac-H3) and methylation of histone H3 (met-H3) in ARPE-19 and 661W cells.

LSD1/HDAC-IN-3 (Compound (±)-3d) at a concentration of 10 μM (1 μL/eye), administered via intravitreal injection as a single bilateral dose, can enhance the survival of photoreceptors in the retinal tissue of rd10 mice with a C57Bl/6J background.