TAK-418 is a selective and orally active inhibitor of LSD1/KDM1A enzyme with an IC50 of 2.9 nM. TAK-418 unlocks abnormal epigenetic mechanisms and improves autism symptoms in models of neurodevelopmental disorders.

LSD1/KDM1A:2.9 nM

TAK-418 (1 mg/kg; oral; once daily for 14 days) improves certain autism spectrum disorder (ASD)-like behaviors in rodents that model neurodevelopmental disorders.[1]
TAK-418 increases H3K4me1/2/3 and H3K9me2 levels of the Ucp2 gene and induces Ucp2 mRNA expression in primary cultured rat neurons. TAK-418 also increases H3K4me1/2/3 of the Bdnf gene. TAK-418 avoids steric interference of GFI1B in the binding pocket by generating a tightly formylated adduct form of coenzyme flavin adenine dinucleotide (FAD). TAK-418 exhibits favorable pharmacokinetic profiles in rodents and inhibits LSD1 enzymatic activity in the brain without causing hematological toxicity in rodents.[1]
A single administration of 1 or 3 mg/kg of TAK-418 increases H3K4me2 levels of the Ucp2 gene in the mouse brain.[1]
TAK-418 can improve neurological problems at cellular, molecular, gene expression, functional, and functional levels in the KS mouse model (Kmt2d+/βGeo mice).[2]