TAK-418 free base
Based on 2 publication(s) in Google Scholar
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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- CAS No.: 1818252-52-6
- 화학식: C17H24N2O2S
- 분자량:320.45
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
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- References
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Publications Citing Use of MedChemExpress (MCE) TAK-418 free base
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Biological Activity
제품 설명
IC50 & Target
[2]|
LSD1 2.9 nM (IC50) |
In Vitro
TAK-418 (10 μM; 1 h) free base engages its cellular target LSD1 in TF-1a cells, as demonstrated by increased thermal stability of the protein[1].
TAK-418 free base is a specific inhibitor of LSD1 enzyme activity with an IC50 of 2.9 nM[2].
TAK-418 (40 min) free base inhibits LSD1 demethylase activity in the HTRF-based assay[2].
TAK-418 (1-3 days) free base increases histone methylation at the Ucp2 gene in primary cultured rat neurons[2].
TAK-418 (1-3 days) free base increases histone methylation at the Bdnf gene in primary cultured rat neurons[2].
TAK-418 (3 days) free base induces Ucp2 mRNA expression in primary cultured rat neurons[2].
TAK-418 free base has minimal impact on the LSD1-GFI1B interaction in TF-1a cells[2].
TAK-418 (1 mM; 1 h) free base forms a compact formylated FAD adduct in LSD1 protein[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:primary cultured rat neurons
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Concentration:0.0001, 0.001, 0.01, 0.1, 1 and 10 μM
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Incubation Time:3 days
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Result:Increased H3K4me2 and H3K9me2 at the Ucp2 gene and induced Ucp2 mRNA expression.
Increased H3K4me1/2/3 at the Bdnf gene.
In Vivo
TAK-418 (1 mg/kg; p.o.; once daily; 14 days) free base does not improve memory, sociability, or sensorimotor gating deficits in miR-137 Tg mice[1].
TAK-418 (1 mg/kg; p.o.; once daily; 14 days) free base restores dysregulated gene expression and DNA methylation, and ameliorates social deficits and cognitive impairment in VPA (HY-10585)-induced ASD model rats[2].
TAK-418 (0.1-1 mg/kg; p.o.; once daily; 14 days) free base improves social behavior in poly I:C (HY-107202)-induced ASD model mice and restores dysregulated gene expression and DNA methylation to normal levels[2].
TAK-418 (1 mg/kg; p.o.; single administration or once daily for 14 days) free base does not affect cognitive function in normal healthy rats[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (aged male, 11-14 months old at purchase; 16 months old at testing)[1]
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Dosage:0.1 or 0.3 mg/kg
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Administration:p.o.; once daily; 4 days
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Result:Improved recognition memory in aged mice, as assessed by the NOR test.
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Animal Model:Tg2576 (female, 9 months old)[1]
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Dosage:0.1 or 0.3 mg/kg
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Administration:p.o.; once daily; 4 days
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Result:Improved recognition memory deficits in Tg2576 mice at 0.3 mg/kg.
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Animal Model:miR-137 transgenic (4 months old)[1]
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Dosage:1 mg/kg
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Administration:p.o.; once daily; 14 days
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Result:Did not improve memory function in miR-137 Tg mice, as assessed by NOR tests.
Did not rescue sociability deficits or sensorimotor gating abnormalities.
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Animal Model:Sprague-Dawley (SD) (male, juvenile and adult, maternal VPA exposure)[2]
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Dosage:1 mg/kg
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Administration:p.o.; once daily; 14 days (sociability, repetitive behavior, RNA-seq, ChIP-seq, RRBS); single administration (sociability); 1 week (sociability); 16-20 days (cognition)
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Result:Showed 95.7% inhibition of LSD1 enzyme activity.
Completely recovered sociability in juvenile VPA rats at 1 mg/kg.
Completely recovered sociability in adult VPA rats at 1 mg/kg.
Recovered sociability in juvenile VPA rats after 1-week QD administration.
Significantly rescued decreased novelty discrimination index (NDI) in 6-week-old VPA rats after 16-20 days QD administration.
Observed inverse correlation between disease-induced changes and TAK-418 effects with correlation coefficients of -0.912 (juvenile) and -0.928 (adult).
Normalized dysregulated patterns of H3K9ac (correlation coefficient = -0.75) and DNA methylation (correlation coefficient = -0.90).
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Animal Model:C57BL/6J (male, adult, maternal poly I:C exposure)[2]
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Dosage:0.1-1 mg/kg
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Administration:p.o.; QD; 14 days
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Result:Showed 91.5% inhibition of LSD1 enzyme activity.
Significantly increased the sniffing index at 0.1, 0.3, or 1 mg/kg.
Observed inverse correlation between disease-induced changes and TAK-418 effects with a correlation coefficient of -0.958.
Normalized dysregulated patterns of DNA methylation with a correlation coefficient of -0.96.
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Animal Model:Long-Evans (male, 7-week-old, naive)[2]
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Dosage:1 mg/kg
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Administration:p.o.; single administration or QD; 14 days
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Result:Had no effects on delay-dependent forgetting of object memory.
Chemical Information
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CAS No. 1818252-52-6
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분자량 320.45
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화학식 C17H24N2O2S
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SMILES
O=C(NC1CCOCC1)C2=CSC([C@H](C3)[C@@H]3NCC4CC4)=C2
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
Publications (2)
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Journal Impact Factor
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Most Recent
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Nature
Perturbing LSD1 and WNT rewires transcription to synergistically induce AML differentiation. [Abstract]2025 Jun;642(8067):508-518. PMID: 40240608 -
Proc Natl Acad Sci U S A
2025 May 20;122(20):e2425812122. PMID: 40366693
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
TAK-418 free base Related Classifications
HY-138830B Related Classifications
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