For research use only. Not for therapeutic Use.
TAK-418 is a selective, orally active LSD1 (KDM1A) enzyme inhibitor with an IC50 of 2.9 nM. TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models[1][2].
TAK-418 (1 mg/kg; p.o.; once daily for 14 days) ameliorates some autism spectrum disorder (ASD) -like behaviors in neurodevelopmental disorder model rodents[1].
TAK-418 increases H3K4me1/2/3 and H3K9me2 levels at the Ucp2 gene and induced Ucp2 mRNA expression in primary cultured rat neurons. TAK-418 also increases H3K4me1/2/3 at the Bdnf gene. TAK-418 avoids the steric interference with GFI1B in the binding pocket through the generation of a compact formylated adduct form of coenzyme flavin adenine dinucleotide (FAD). TAK-418 shows a good pharmacokinetic profile in rodents and inhibits LSD1 enzyme activity in the brain without causing hematological toxicity in rodents[1].
Single administration of TAK-418 at 1 or 3 mg/kg increases H3K4me2 levels at Ucp2 gene in the mouse brain[1].
TAK-418 can ameliorate neurological problems at the cellular, molecular, gene expression, and functional levels in a mouse model of KS (Kmt2d+/βGeo mice)[2].
| Catalog Number | I036962 |
| CAS Number | 1818252-53-7 |
| Synonyms | 5-[(1R,2R)-2-(cyclopropylmethylamino)cyclopropyl]-N-(oxan-4-yl)thiophene-3-carboxamide;hydrochloride |
| Molecular Formula | C17H25ClN2O2S |
| Purity | ≥95% |
| InChI | InChI=1S/C17H24N2O2S.ClH/c20-17(19-13-3-5-21-6-4-13)12-7-16(22-10-12)14-8-15(14)18-9-11-1-2-11;/h7,10-11,13-15,18H,1-6,8-9H2,(H,19,20);1H/t14-,15-;/m1./s1 |
| InChIKey | LEEWMGOHGNRDKC-CTHHTMFSSA-N |
| SMILES | C1CC1CNC2CC2C3=CC(=CS3)C(=O)NC4CCOCC4.Cl |
| Reference | [1]. Baba R, et al. LSD1 enzyme inhibitor TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models. Sci Adv. 2021;7(11):eaba1187. Published 2021 Mar 12. [2]. Zhang L, et al. Inhibition of KDM1A activity restores adult neurogenesis and improves hippocampal memory in a mouse model of Kabuki syndrome. Mol Ther Methods Clin Dev. 2021;20:779-791. Published 2021 Feb 18 |
