GSK1034702 hydrochloride
GSK1034702 hydrochloride is an orally active and allosteric agonist of M1 mAChR (pEC50=8.1) that can cross the blood-brain barrier. GSK1034702 hydrochloride activates the Gq/11 protein-mediated signaling pathway, enhancing neuronal firing and long-term potentiation (LTP) in the CA1 region of the hippocampus. GSK1034702 hydrochloride can modulate hippocampal function, improve memory encoding in the nicotine withdrawal cognitive dysfunction model, and show pro-cognitive effects in rodents. GSK1034702 hydrochloride can be used for the study of the mechanisms of cognitive impairment diseases such as Alzheimer's disease, and has certain peripheral M receptor activation-related side effects (such as gastrointestinal reactions).
For research use only. We do not sell to patients.
- CAS No.: 932373-86-9
- Formula: C18H25ClFN3O2
- Molecular Weight:369.86
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Radioligand binding assay
GSK1034702 hydrochloride (1 nM-10 μM; overnight) competitively inhibits [3H]-NMS binding in CHO cells expressing human M1 mAChR with a pKi of 6.5, and binding to M1 receptors is not affected by DREADD mutations (Y106C/A196G)[1].
Inositol phosphate (IP) accumulation assay
GSK1034702 hydrochloride (0.1 nM-10 μM; 45 min) concentration-dependently stimulates M1 receptor-mediated inositol phosphate 1 accumulation in CHO cells with an EC50 of 7.1 nM and a maximal effect of 90% of ACh[1].
ERK1/2 phosphorylation assay
GSK1034702 hydrochloride (0.1 nM-10 μM; 5 min) activates M1 receptor-mediated ERK1/2 phosphorylation in CHO cells[1].
In vitro tissue function assay
GSK1034702 hydrochloride inhibits the contraction induced by Methacholine (HY-A0083) (IC50=8 μM), stimulates approximately 50% of the maximum Methacholine-induced contraction in rat ileum (EC50=7 μM), and inhibits Methacholine-induced contraction (IC50=46 μM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
GSK1034702 (0.3-30 mg/kg; intraperitoneal injection; single dose) hydrochloride improves memory in a dose-dependent manner in the contextual fear conditioning model induced by 1.5 mg/kg Scopolamine (HY-N0296) in mice; 10 mg/kg dose reversed memory deficits[1].
Neuron discharge enhancement experiment
GSK1034702 (1-10 mg/kg; intraperitoneal injection; acute or 7-day subchronic) hydrochloride increases neuronal discharge rate by 42% in the Wistar rat hippocampal model after acute administration of 10 mg/kg; subchronic administration (6 mg/kg/d) sustainedly enhances discharge and reversed Scopolamine (HY-N0296)-induced passive avoidance memory deficits[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 male mice (8-12 weeks, 20-25 g) with Scopolamine-induced amnesia[1]
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Dosage:0.3, 1, 3, 10, 30 mg/kg (5% glucose) GSK1034702
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Administration:Single i.p. injection 30 min before scopolamine (1.5 mg/kg) and training
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Result:Increased immobility time from 12.3 s to 15.6 s at 10 mg/kg, reversing Scopolamine-induced memory impairment.
Chemical Information
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CAS No. 932373-86-9
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Molecular Weight 369.86
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Formula C18H25ClFN3O2
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SMILES
O=C1NC2=C(C=C(C)C=C2N1C3CCN(C4CCOCC4)CC3)F.Cl
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Bradley SJ, et al. Bitopic Binding Mode of an M1 Muscarinic Acetylcholine Receptor Agonist Associated with Adverse Clinical Trial Outcomes. Mol Pharmacol. 2018 Jun;93(6):645-656. [Content Brief]
[2]. Nathan PJ, et al. The potent M1 receptor allosteric agonist GSK1034702 improves episodic memory in humans in the nicotine abstinence model of cognitive dysfunction. Int J Neuropsychopharmacol. 2013 May;16(4):721-31. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
GSK1034702 hydrochloride Related Classifications
HY-107111A Related Classifications
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