TAK-418
Based on 2 publication(s) in Google Scholar
TAK-418 is an orally active, blood-brain barrier-penetrant LSD1 inhibitor with a human IC50 of 2.9 nM. TAK-418 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 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 rescues defective H3K4 histone modifications, normalizes adult neurogenesis, and improves recognition memory, social behavior, and cognition in rodent models. TAK-418 can be used in research related to neurodevelopmental disorders, Alzheimer's disease, and autism spectrum disorders.
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度 : 99.81%
- CAS 番号: 1818252-53-7
- 分子式: C17H25ClN2O2S
- 分子量:356.91
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保管条件:
-20°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
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溶剤 & 溶解度
- プロトコル
- 純度とドキュメンテーション
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Help & FAQs
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MedChemExpress（MCE）の使用を引用している文献 TAK-418
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生物活性
製品説明
IC50 & Target
[2]|
LSD1 2.9 nM (IC50) |
体外実験
TAK-418 (free base) is a specific inhibitor of LSD1 enzyme activity with an IC50 of 2.9 nM[2].
TAK-418 (free base) (40 min) inhibits LSD1 demethylase activity in the HTRF-based assay[2].
TAK-418 (free base) (1 or 3 days) increases histone methylation at the Ucp2 gene in primary cultured rat neurons[2].
TAK-418 (free base) (1 or 3 days) increases histone methylation at the Bdnf gene in primary cultured rat neurons[2].
TAK-418 (free base) (3 days) 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 (free base) (1 mM; 1 h) 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.
体内実験
TAK-418 (1 mg/kg; p.o.; once daily; 14 days) 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) 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) 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) 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.
臨床実験
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | 2011-05 | PHASE1 |
化学情報
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CAS 番号 1818252-53-7
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性状 Solid-Liquid Mixture
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分子量 356.91
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分子式 C17H25ClN2O2S
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Color White to yellow
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SMILES
O=C(C1=CSC([C@H]2[C@H](NCC3CC3)C2)=C1)NC4CCOCC4.[H]Cl
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
-20°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
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
溶剤 & 溶解度
体外:
DMSO : 55 mg/mL (154.10 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
H2O : ≥ 16.67 mg/mL (46.71 mM)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
体内:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 5.5 mg/mL (15.41 mM); Clear solution
This protocol yields a clear solution of ≥ 5.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (55.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 5.5 mg/mL (15.41 mM); Clear solution
This protocol yields a clear solution of ≥ 5.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (55.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
純度とドキュメンテーション
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データシート (292 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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取扱説明書 (2659 KB)
参考文献
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| H2O / DMSO | 1 mM | 2.8018 mL | 14.0091 mL | 28.0183 mL | 70.0457 mL |
| 5 mM | 0.5604 mL | 2.8018 mL | 5.6037 mL | 14.0091 mL | |
| 10 mM | 0.2802 mL | 1.4009 mL | 2.8018 mL | 7.0046 mL | |
| 15 mM | 0.1868 mL | 0.9339 mL | 1.8679 mL | 4.6697 mL | |
| 20 mM | 0.1401 mL | 0.7005 mL | 1.4009 mL | 3.5023 mL | |
| 25 mM | 0.1121 mL | 0.5604 mL | 1.1207 mL | 2.8018 mL | |
| 30 mM | 0.0934 mL | 0.4670 mL | 0.9339 mL | 2.3349 mL | |
| 40 mM | 0.0700 mL | 0.3502 mL | 0.7005 mL | 1.7511 mL | |
| DMSO | 50 mM | 0.0560 mL | 0.2802 mL | 0.5604 mL | 1.4009 mL |
| 60 mM | 0.0467 mL | 0.2335 mL | 0.4670 mL | 1.1674 mL | |
| 80 mM | 0.0350 mL | 0.1751 mL | 0.3502 mL | 0.8756 mL | |
| 100 mM | 0.0280 mL | 0.1401 mL | 0.2802 mL | 0.7005 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
TAK-418 関連分類
HY-138830 関連分類
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