1818252-52-6
Chemical Structure
TAK-418 free base
- CAS. Nr.: 1818252-52-6
- Formula:C17H24N2O2S
- Molecular Weight:320.45
InChIKey: QZNGFWQWWSECMG-HUUCEWRRSA-N
SMILES: O=C(NC1CCOCC1)C2=CSC([C@H](C3)[C@@H]3NCC4CC4)=C2
Biological Activity: TAK-418 free base is an orally active, blood-brain barrier-penetrant LSD1 inhibitor with a human IC50 of 2.9 nM. TAK-418 free base irreversibly inhibits LSD1 by forming a compact flavin-FAD adduct with the catalytic domain FAD, blocking the demethylation of H3K4me1/2 and H3K9me1/2 without disrupting the LSD1-GFI1B interaction. TAK-418 free base restores normally dysregulated brain gene expression and DNA methylation, increases H3K4me1/2/3 and H3K9me2 at the Ucp2 locus, and induces Ucp2 mRNA expression. TAK-418 free base rescues defective H3K4 histone modifications, normalizes adult neurogenesis, and improves recognition memory, social behavior, and cognition in rodent models. TAK-418 free base can be used in research related to neurodevelopmental disorders, Alzheimer's disease, and autism spectrum disorders[1][2][3].
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TAK-418 free base | TAK-418 free base is an orally active, blood-brain barrier-penetrant LSD1 inhibitor with a human IC50 of 2.9 nM. TAK-418 free base irreversibly inhibits LSD1 by forming a compact flavin-FAD adduct with the catalytic domain FAD, blocking the demethylation of H3K4me1/2 and H3K9me1/2 without disrupting the LSD1-GFI1B interaction. TAK-418 free base restores normally dysregulated brain gene expression and DNA methylation, increases H3K4me1/2/3 and H3K9me2 at the Ucp2 locus, and induces Ucp2 mRNA expression. TAK-418 free base rescues defective H3K4 histone modifications, normalizes adult neurogenesis, and improves recognition memory, social behavior, and cognition in rodent models. TAK-418 free base can be used in research related to neurodevelopmental disorders, Alzheimer's disease, and autism spectrum disorders. | |||||||||||||||||||||
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References
- [1]. Baba R, et al. Investigating the Therapeutic Potential of LSD1 Enzyme Activity-Specific Inhibition by TAK-418 for Social and Memory Deficits in Rodent Disease Models. ACS chemical neuroscience. 2022 Feb 02;13(3):313-321.
- [2]. Baba R, et al. LSD1 enzyme inhibitor TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models. Science advances. 2021 Mar;7(11):eaba1187. [Content Brief]
- [3]. Yin W, et al. Safety, pharmacokinetics and pharmacodynamics of TAK-418, a novel inhibitor of the epigenetic modulator lysine-specific demethylase 1A. British journal of clinical pharmacology. 2021 Dec;87(12):4756-4768.
