A-3190
A-3190 is an orally active, blood-brain barrier permeable CD38 inhibitor, with an IC50 of 7.25 nM against human CD38 and 1.24 nM against mouse CD38. A-3190 is a derivative of A-8531 (HY-184021), and it forms covalent adducts with NAD+ in the presence of CD38. A-3190 acts as an inducer of NAD+ levels and an inhibitor of NAM and ADPR levels. A-3190 increases NAD+ levels in the skin, lung, liver and brain of rodents, while reducing NAM and ADPR levels in brain tissues. A-3190 can be used in research related to multiple sclerosis, Parkinson's disease and Alzheimer's disease.
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- Formule: C17H13N5O2S2
- Masse moléculaire:383.45
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Stockage:
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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Activité biologique
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Chemical Information
- Protocole
- Pureté et documentation
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Help & FAQs
Activité biologique
Description
In Vitro
A-3190 (compound 39) (1 μM; 1-2 h) potently inhibits human CD38 with an IC50 of 7.25 nM and mouse CD38 with an IC50 of 1.24 nM in a biochemical etheno-NAD hydrolase inhibition assay[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
A-3190 (30 mg/kg; p.o.; single dose) maintains unbound plasma concentrations above the mouse CD38 IC50 for over 24 hours and achieves moderate brain penetration[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; 3 mg/kg; 10 mg/kg; 30 mg/kg
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Administration:p.o.; daily; 4 days
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Result:Increased NAD+ levels in a dose-dependent manner in skin, lung, liver, and brain.
Significantly increased NAD+ levels relative to vehicle at 3, 10, and 30 mg/kg in skin, lung; at 1, 3, 10, and 30 mg/kg in liver and brain.
Reached unbound tissue concentrations up to ~1000-fold over the mouse CD38 IC50 at 30 mg/kg in skin, lung, and liver.
Decreased nicotinamide (NAM) and adenosine diphosphate ribose (ADPR) levels in a dose-dependent manner in brain, with significant reductions relative to vehicle seen at 1, 3, 10, and 30 mg/kg.
Reached unbound brain concentrations up to ~80-fold over the mouse CD38 IC50 at 30 mg/kg.
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Animal Model:CD-1 (male, 25-40 g, 31-44 days old)[1]
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Dosage:30 mg/kg
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Administration:p.o.; single dose
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Result:Maintained unbound plasma concentrations above the mouse CD38 IC50 for more than 24 hours post-dose.
Achieved an unbound brain-to-plasma ratio of 0.12 at 3 hours post-dose and 0.11 at 24 hours post-dose.
Chemical Information
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Masse moléculaire 383.45
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Formule C17H13N5O2S2
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SMILES
O=S(N1N=CC(C2=NC3=C(SC=C3C4=CC=NC=C4)C=N2)=C1)(C5CC5)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocole
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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.
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Human pluripotent stem cell midbrain dopaminergic neuron differentiation
Human pluripotent stem cells are directed toward midbrain dopaminergic neurons by first inducing a neural floor-plate-like progenitor state, then patterning cells with ventralizing SHH signaling and midbrain/WNT-FGF cues, and finally maturing progenitors into neurons expressing dopaminergic markers such as TH, NURR1/NR4A2, PITX3, DAT/SLC6A3, VMAT2/SLC18A2, GIRK2/KCNJ6, FOXA2, LMX1A, and EN1. The main readouts are loss of pluripotency, acquisition of FOXA2+/LMX1A+ midbrain floor-plate progenitors, emergence of βIII-tubulin+/MAP2+ neurons, and production of TH+ dopaminergic neurons with molecular, dopamine-release, and electrophysiological features of midbrain dopaminergic identity.
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Alzheimer’s Disease Modeling
Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive functions and loss of specific types of neurons and synapses. Alzheimer's symptoms can be simulated in mice by injecting drugs (such as Aβ) or genetically modified.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
A-3190 Related Classifications
HY-184206 Related Classifications
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