A-8531
A-8531 is an orally active CD38 inhibitor with IC50 values of 1.10 nM against human CD38, IC50 values of 2.93 nM against mouse CD38, and a human Ka of 0.32 nM. A-8531 exerts its inhibitory activity via its 4-pyridine reactive warhead interacting with the CD38 substrate NAD+, and binds stably to CD38 only in the presence of NAD+, with a binding KD of 0.32 nM as detected by SPR. A-8531 dose-dependently increases NAD+ levels in mouse skin, lung and liver tissues, while simultaneously reducing the contents of NAM and ADPR in these tissues. A-8531 derivative A-3190 (HY-184206) has blood-brain barrier penetration. A-8531 can be used in studies related to neurodegenerative diseases.
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。
- 分子式: C22H20N6O
- 分子量:384.43
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
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
- プロトコル
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
製品説明
体外実験
A-8531 (compound 25) (0-1 μM; 1-2 h) potently inhibits human CD38 NADase activity with an IC50 of 0.311 nM, and potently inhibits mouse CD38 NADase activity with an IC50 of 3.12 nM[1].
A-8531 binds tightly to human CD38 only in the presence of NAD+, with a KD value of 0.32 nM[1].
A-8531 significantly stabilizes human CD38 (ΔTm = 17.0 °C) only when incubated with 1 mM NAD+[1].
A-8531 is a non-competitive inhibitor of human CD38 hydrolase activity, with a Kiu of 0.6 nM[1].
A-8531 exhibits an apparent permeability coefficient of 51.3 × 10-6 cm/s in MDCK-MDR1 cells with a high efflux ratio of 5.8[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
体内実験
A-8531 (30 mg/kg; p.o.; once; daily; 4 days) produces peak lung NAD+ elevation at 3 hours post-dose, with no compound or NAD+ accumulation after 4 days of daily dosing[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57Bl/6J (female, average 20 g, 11-14 weeks of age)[1]
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Dosage:1 mg/kg; 10 mg/kg; 30 mg/kg
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Administration:p.o.; daily; 4 days
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Result:Elevated NAD+ in skin, lung and liver at 1 mg/kg, with free tissue exposures ~10× (skin), ~10× (lung), ~12× (liver) mouse CD38 IC50.
Boosted NAD+ in skin, lung and liver at 10 mg/kg, with free tissue exposures >100× (skin), ~70× (lung), >100× (liver) mouse CD38 IC50.
Attained free brain concentrations 3.5× mouse CD38 IC50 at 30 mg/kg, yielding brain NAD+ comparable to 1 mg/kg A-3190.
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Animal Model:C57Bl/6J (female, average 20 g, 11-14 weeks of age)[1]
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Dosage:30 mg/kg
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Administration:p.o.; once; p.o.; daily; 4 days
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Result:Produced peak NAD+ levels in lung tissue at 3 hours post-dose for both single and 4-day daily dosing, with significant elevations.
Decreased NAD+ levels and unbound lung tissue concentrations sharply between 6 and 24 hours post-dose.
Showed no accumulation of compound or NAD+ between single and 4-day daily dosing.
化学情報
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分子量 384.43
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分子式 C22H20N6O
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SMILES
NC1=C(C2=CC=NC=C2)N3N=C(C4=CC=C(C(N(C)C5CC5)=O)C=C4)C=CC3=N1
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
プロトコル
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
A-8531 関連分類
HY-184021 関連分類
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