GSK1034702
Based on 1 Customer Validation
GSK1034702 is an orally active and allosteric agonist of M1 mAChR (pEC50=8.1) that can cross the blood-brain barrier. GSK1034702 activates the Gq/11 protein-mediated signaling pathway, enhancing neuronal firing and long-term potentiation (LTP) in the CA1 region of the hippocampus. GSK1034702 can modulate hippocampal function, improve memory encoding in the nicotine withdrawal cognitive dysfunction model, and show pro-cognitive effects in rodents. GSK1034702 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).
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- Purity: 99.78%
- CAS No.: 932373-87-0
- 화학식: C18H24FN3O2
- 분자량:333.40
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보관:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
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Biological Activity
Radioligand binding assay
GSK1034702 (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 (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 (0.1 nM-10 μM; 5 min) activates M1 receptor-mediated ERK1/2 phosphorylation in CHO cells[1].
In vitro tissue function assay
GSK1034702 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) 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) 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)
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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.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 932373-87-0
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Appearance Solid
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분자량 333.40
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화학식 C18H24FN3O2
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Color White to off-white
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SMILES
CC1=CC2=C(NC(N2C3CCN(C4CCOCC4)CC3)=O)C(F)=C1
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
DMSO : 2 mg/mL (6.00 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
순도&문서
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Data Sheet (276 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Handling Instructions (2659 KB)
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]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.9994 mL | 14.9970 mL | 29.9940 mL | 74.9850 mL |
| 5 mM | 0.5999 mL | 2.9994 mL | 5.9988 mL | 14.9970 mL |
GSK1034702 Related Classifications
HY-107111 Related Classifications
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