TAK-418 (TAK418) is a potent, specific inhibitor of LSD1 (KDM1A) enzyme activity with IC50 of 2.9 nM.
TAK-418 does not inhibit recombinant human MAO-A and MAO-B with IC50 of >100 uM.
TAK-418 (0.1-10 uM) increases H3K4me1/2/3 and H3K9me2 levels at the Ucp2 gene and induces Ucp2 mRNA expression in primary cultured rat neurons, also increases H3K4me1/2/3 at the Bdnf gene.
TAK-418 has minimal impact on the interaction between LSD1 and its cofactor, GFI1B.
Single administration of TAK-418 at 1 or 3 mg/kg increases H3K4me2 levels at Ucp2 gene in the mouse brain.
TAK-418 normalizes mRNA expression dysregulated in neurodevelopmental disorder model rodents.
TAK-418 produces inverse correlation against the histone modification and DNA methylation levels altered in VPA rats and poly I:C mice.
TAK-418 ameliorates some ASD-like behaviors in neurodevelopmental disorder model rodents.
