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.
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- Fòrmula: C22H20N6O
- Peso molecular:384.43
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
- Pureza y Documentación
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Help & FAQs
Actividad biológica
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.
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.
Chemical Information
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Peso molecular 384.43
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Fòrmula 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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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
A-8531 Related Classifications
HY-184021 Related Classifications
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