JWX-A0108
JWX-A0108 is a selective human α7 nAChR positive allosteric modulator with an EC50 of 4.35 μM. JWX-A0108 potentiates α7 nAChR currents only in the presence of acetylcholine, with no direct activating effect or alteration of desensitization. JWX-A0108 enhances hippocampal GABAergic synaptic transmission by increasing spontaneous inhibitory postsynaptic currents. JWX-A0108 reduces the brain expression levels of IL-1β, TNF-α, and IL-6 by blocking the NF-κB signaling pathway, and reduces microglial activation by downregulating Iba1. JWX-A0108 effectively improves cognitive deficits, neuroinflammation, and hippocampal neuronal damage in mouse models of schizophrenia and Alzheimer's disease. JWX-A0108 can be used for research related to schizophrenia and Alzheimer's disease.
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- No. CAS: 2055045-42-4
- Fòrmula: C19H14ClFN4OS
- Peso molecular:400.86
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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
- Referencias
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Help & FAQs
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Actividad biológica
Descripciòn
IC50 & Target
[3]|
IL-1β |
TNF-α |
NF-κB |
In Vitro
JWX-A0108 (0.1-30 μM; 2-5 days) selectively enhances α7 nAChR-mediated currents in Xenopus laevis oocytes expressing human α7 nAChR, with an EC50 of 4.35 μM, and shows no activity on other tested nAChR subtypes or 5-HT3A receptors[1].
JWX-A0108 potently enhances acetylcholine-activated current in Xenopus oocytes expressing human α7 nAChR as a type I positive allosteric modulator with an EC50 of 5.7 μM and 6-fold current amplification[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
In Vivo
JWX-A0108 (5 mg/kg; i.p.; once daily; for 19 consecutive days) improves spatial memory impairment (reduced escape latency) in APP/PS1 mice, alleviates neuroinflammation via inhibition of the α7 nAChR-mediated NF-κB signaling pathway, and protects hippocampal neurons[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 (male, adult)[1]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:i.p.
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Result:Reversed Dizocilpine-induced percent prepulse inhibition (PPI) reduction from 19% to 25% (1 mg/kg), 32% (3 mg/kg), and 37% (10 mg/kg) across five prepulse intensities.
Significantly increased average percent PPI across all prepulse levels in a dose-dependent manner compared to the MK-801-only group.
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Animal Model:C57BL/6J (male, adult)[1]
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Dosage:0.03 mg/kg; 0.1 mg/kg; 0.3 mg/kg
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Administration:i.p.
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Result:Reversed Dizocilpine-induced reduction of time spent in the novel arm from 45% to 49% (0.03 mg/kg), 53% (0.1 mg/kg), and 61% (0.3 mg/kg).
Attenuated Dizocilpine-induced increase in total travel distance at the 0.03 mg/kg dose.
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Animal Model:APP/PS1 double transgenic mice (9-month-old, on C57BL/6J background)[2]
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Dosage:5 mg/kg
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Administration:i.p.; daily; 19 days
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Result:Shortened escape latency of APP/PS1 mice in the Morris Water Maze test.
Reduced mRNA and protein levels of pro-inflammatory cytokines IL-1β, TNF-α, and IL-6 in cerebral cortex and hippocampus.
Decreased protein expression and hippocampal fluorescence intensity of microglial activation marker Iba1.
Improved hippocampal CA3 region neuronal damage with increased Nissl body counts and reduced vacuolar degeneration.
Reduced phosphorylation levels of NF-κB p65 (Ser536) and IκBα (Ser32/36).
Chemical Information
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No. CAS 2055045-42-4
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Peso molecular 400.86
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Fòrmula C19H14ClFN4OS
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SMILES
O=C1C2=C(N=CN1C3=C(C)C=CC=C3Cl)N=C(NC4=CC=C(C)C(F)=C4)S2
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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
[1]. Sun LL, et al. Pharmacological characterization of JWX-A0108 as a novel type I positive allosteric modulator of α7 nAChR that can reverse acoustic gating deficits in a mouse prepulse inhibition model. Acta Pharmacol Sin. 2019;40(6):737-745. [Content Brief]
[2]. Li H, et al. JWX-A0108, a positive allosteric modulator of α7 nAChR, attenuates cognitive deficits in APP/PS1 mice by suppressing NF-κB-mediated inflammation. Int Immunopharmacol. 2021;96:107726. [Content Brief]
Calculators
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