| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
M1 muscarinic acetylcholine receptor (M1 mAChR). GSK-1034702 is an allosteric agonist of M1 mAChR. It activates the Gq/11 protein-mediated signaling pathway.
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| ln Vitro |
In vitro, GSK-1034702 acts as an M1 mAChR allosteric agonist with a pEC₅₀ of 8.1. It activates Gq/11 protein-mediated signaling pathways in cells expressing M1 receptors. The compound enhances neuronal firing and long-term potentiation (LTP) in the CA1 region of the hippocampus in electrophysiological recordings.
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| ln Vivo |
In vivo, GSK-1034702 modulates hippocampal function and improves memory encoding in the nicotine withdrawal cognitive dysfunction model. It shows pro-cognitive effects in rodents and can be used for studying the mechanisms of cognitive impairment diseases such as Alzheimer's disease. The compound is orally active and brain-penetrant.
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| Enzyme Assay |
Non-cell binding assays for GSK-1034702 are performed using membrane preparations from cells expressing human M1 mAChR. Radioligand binding studies are conducted using [³H]N-methylscopolamine or [³H]QNB as tracers to assess orthosteric binding. Allosteric binding is assessed using [³H]dimethyl-W84 or other allosteric radioligands. Membranes are incubated with the radioligand and varying concentrations of GSK-1034702 (0.001-100 μM). Nonspecific binding is determined with atropine. Filtration and scintillation counting follow incubation.
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| Cell Assay |
Cellular assays are performed using CHO or HEK-293 cells stably expressing M1 mAChR. Calcium flux assays are conducted using calcium-sensitive fluorescent dyes (e.g., Fluo-4). Cells are loaded with dye, and GSK-1034702 is added at concentrations ranging from 0.001-100 μM. Fluorescence changes are measured in a plate reader. The pEC₅₀ for calcium mobilization is determined. Gq/11-mediated signaling is confirmed using specific inhibitors.
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| Animal Protocol |
In vivo studies are conducted in rodent models of cognitive dysfunction, including the nicotine withdrawal cognitive impairment model. GSK-1034702 is administered orally at doses typically ranging from 0.1-10 mg/kg. Cognitive performance is assessed using behavioral tests such as novel object recognition, Morris water maze, or radial arm maze. Hippocampal LTP is measured using in vivo electrophysiology. Brain and plasma concentrations are determined by LC-MS/MS.
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| ADME/Pharmacokinetics |
GSK-1034702 is orally active and can cross the blood-brain barrier. The compound shows good oral bioavailability in preclinical species. It is metabolized primarily by hepatic cytochrome P450 enzymes. The half-life in rodents is sufficient for once- or twice-daily dosing in efficacy studies. Further detailed PK parameters are available in proprietary GSK research reports.
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| Toxicity/Toxicokinetics |
In preclinical studies, GSK-1034702 has certain peripheral M receptor activation-related side effects such as gastrointestinal reactions. No significant central nervous system toxicity has been reported at therapeutic doses. Standard safety pharmacology studies would be required for therapeutic development. The compound is generally well-tolerated at doses effective for cognitive enhancement.
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| References |
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| Additional Infomation |
Gsk1004723 has been studied for the treatment of allergic rhinitis and seasonal allergic rhinitis.
GSK-1034702 was developed by GlaxoSmithKline as a cognitive enhancer targeting M1 mAChR. The M1 receptor is a promising target for Alzheimer's disease and other cognitive disorders. The compound's allosteric mechanism offers the advantage of receptor subtype selectivity compared to orthosteric agonists. GSK-1034702 has been used in preclinical research to validate M1 mAChR as a therapeutic target for cognitive impairment. It is not approved for clinical use. |
| Molecular Formula |
C18H24FN3O2
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|---|---|
| Molecular Weight |
333.40046787262
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| Exact Mass |
333.185
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| Elemental Analysis |
C, 64.84; H, 7.26; F, 5.70; N, 12.60; O, 9.60
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| CAS # |
932373-87-0
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| Related CAS # |
932373-87-0;932373-86-9 (HCl);
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| PubChem CID |
17747460
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| Appearance |
White to off-white solid powder
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| LogP |
2.53
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
46
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| Complexity |
938
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| Defined Atom Stereocenter Count |
1
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| SMILES |
FC1=CC(C)=CC2=C1NC(N2C1CCN(CC1)C1CCOCC1)=O
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| InChi Key |
YANGEESWIGIKOP-UUWRZZSWSA-N
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| InChi Code |
InChI=1S/C39H49ClN4O2/c40-33-19-15-32(16-20-33)29-38-36-13-3-4-14-37(36)39(45)44(41-38)30-34-12-9-27-43(34)26-8-5-11-31-17-21-35(22-18-31)46-28-10-25-42-23-6-1-2-7-24-42/h3-4,13-22,34H,1-2,5-12,23-30H2/t34-/m1/s1
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| Chemical Name |
2-[[(2R)-1-[4-[4-[3-(azepan-1-yl)propoxy]phenyl]butyl]pyrrolidin-2-yl]methyl]-4-[(4-chlorophenyl)methyl]phthalazin-1-one
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| Synonyms |
GSK-1034702; GSK1034702; GSK 1034702; GSK-1034702 HCl.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~2 mg/mL (~6.00 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9994 mL | 14.9970 mL | 29.9940 mL | |
| 5 mM | 0.5999 mL | 2.9994 mL | 5.9988 mL | |
| 10 mM | 0.2999 mL | 1.4997 mL | 2.9994 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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