| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
α7 nicotinic acetylcholine receptor (α7 nAChR) - positive allosteric modulator.
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| ln Vitro |
In vitro studies demonstrate that nAChR agonist 1 is a potent, brain-permeable, and orally efficacious positive allosteric modulator (PAM) of the α7 nicotinic acetylcholine receptor (α7 nAChR). The compound modulates α7 nAChR activity with an EC50 of 0.32 μM in human IMR-32 neuroblastoma cells that endogenously express the receptor, as measured by calcium flux assays. Positive allosteric modulation of α7 nAChR enhances the receptor's response to acetylcholine, the endogenous neurotransmitter, without directly activating the receptor itself. This mechanism can enhance cholinergic signaling in the brain, which is relevant for cognitive function and neuroprotection. The compound's brain permeability and oral efficacy make it a valuable tool for studying α7 nAChR function in neurological disorders.
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| ln Vivo |
Acute (single dose) oral treatment of compound 28, a nAChR agonist, before memory acquisition greatly exacerbated the latency and scopolamine-induced 8 amnesia in male Wistar rats at dose levels of 1 and 3 mg/kg. When given right after memory acquisition trials, nAChR agonist 1 also markedly increased discrimination index in memory consolidation paradigms [1]. AUC, Cmax, and F values for nAChR agonist 1 therapy (10 mg/kg; oral) were 63 h μM, 2.3 μM, and 63%, respectively [1]. AUC, Cmax, T1/2, CL, and Vss for nAChR agonist 1 (1 mg/kg; IV) treatment were 1.3 h μM, 0.9 μM, 1.4 h, 31 mL/min/kg, and 3 L/kg, respectively. [1].
In vivo studies have demonstrated that nAChR agonist 1 is orally efficacious in animal models relevant to neurological conditions. The compound's brain permeability allows it to reach the central nervous system following oral administration, making it suitable for studying α7 nAChR-mediated effects on cognition, neuroprotection, and inflammation. The α7 nAChR is a target of interest for Alzheimer's disease, schizophrenia, and other neurological and psychiatric disorders due to its role in cognitive function, cholinergic signaling, and neuroinflammation. The compound's ability to enhance α7 nAChR function suggests potential therapeutic applications for these conditions. |
| Enzyme Assay |
For receptor binding and modulation studies, cell-based assays are performed using cells that express the α7 nAChR, such as human IMR-32 neuroblastoma cells or recombinant cell lines. Cells are treated with nAChR agonist 1 at various concentrations in the presence of a sub-maximal concentration of acetylcholine, and receptor activation is measured by calcium flux using fluorescent calcium indicators (e.g., Fluo-4). The EC50 for potentiation of the acetylcholine response is calculated from dose-response curves. Selectivity over other nicotinic receptor subtypes is assessed using similar assay formats to confirm the compound's specificity for α7 nAChR.
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| Cell Assay |
Cellular assays for nAChR agonist 1 typically involve culturing human IMR-32 neuroblastoma cells or other cell lines expressing α7 nAChR. Cells are loaded with a calcium-sensitive fluorescent dye (e.g., Fluo-4 AM) and then treated with the compound at various concentrations in the presence of a sub-maximal concentration of acetylcholine. Calcium flux is measured using a fluorescence plate reader, and the EC50 for potentiation is calculated. For studies of neuronal function, primary neuronal cultures or brain slices are used to assess the compound's effects on synaptic transmission and plasticity. Cytotoxicity against mammalian cells is assessed in parallel to evaluate selectivity.
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| Animal Protocol |
Animal/Disease Models: Male balb/c (Bagg ALBino) mouse [1]
Doses: 10 mg/kg Route of Administration: PO (pharmacokinetic/PK/PK analysis) Experimental Results: AUC, Cmax, and F values were 63 h μM, 2.3 μM, and 63%, respectively. In vivo efficacy of nAChR agonist 1 is evaluated in animal models of cognitive impairment, neuroinflammation, and neurodegenerative diseases. For Alzheimer's disease research, transgenic mouse models (e.g., APP/PS1 or 5xFAD mice) or pharmacologically induced models of cognitive impairment are used. Mice are treated with the compound via oral administration, and cognitive function is assessed using behavioral tests such as the Morris water maze, novel object recognition, or fear conditioning. Neuroinflammation is assessed by measuring cytokine levels and microglial activation in brain tissues. Neuroprotection is evaluated by measuring neuronal survival and synaptic protein levels. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of nAChR agonist 1 have been characterized to support its use as a research tool and potential therapeutic agent. The compound is brain-permeable and orally bioavailable, which are essential properties for studying central nervous system targets. Key PK parameters including half-life, clearance, volume of distribution, and oral bioavailability are determined using LC-MS/MS analysis of plasma and brain tissue samples following administration. The compound's ability to reach therapeutic concentrations in the brain following oral administration is important for its efficacy in neurological disease models. Detailed PK data are typically available in product documentation and primary literature.
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| Toxicity/Toxicokinetics |
Toxicological evaluation of nAChR agonist 1 is typically conducted in parallel with efficacy studies in animal models. Standard toxicology assessments include in vitro cytotoxicity assays against a panel of mammalian cell lines to determine the compound's selectivity index. In vivo toxicity studies in rodents include acute and repeated-dose toxicity testing, observation of clinical signs, and histopathological examination of major organs. As an α7 nAChR modulator, potential effects on the central nervous system, including seizures, cognitive effects, and autonomic function, are carefully monitored. The compound's safety profile is established to define the therapeutic window for research applications.
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| References | |
| Additional Infomation |
nAChR agonist 1 is a research tool compound used for studying α7 nicotinic acetylcholine receptor function and its role in cognitive function, neuroinflammation, and neurological diseases. The compound is not approved for clinical use and is intended for laboratory research purposes only. Its mechanism of action involves positive allosteric modulation of α7 nAChR, which enhances the receptor's response to acetylcholine and potentiates cholinergic signaling in the brain. This compound is valuable for investigating the therapeutic potential of α7 nAChR modulation in Alzheimer's disease, schizophrenia, and other neurological and psychiatric disorders.
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| Molecular Formula |
C20H18CLNO3S2
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|---|---|
| Molecular Weight |
419.944821834564
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| Exact Mass |
419.041
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| Elemental Analysis |
C, 57.20 H, 4.32 Cl, 8.44 N, 3.34 O, 11.43 S, 15.27
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| CAS # |
1394371-75-5
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| Related CAS # |
1394371-75-5;
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| PubChem CID |
60167958
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| Appearance |
Off-white to yellow solid powder
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| LogP |
4.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
620
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
DYIIYIJHDMIABW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H18ClNO3S2/c1-3-17(23)20-18(13-6-10-16(11-7-13)27(22,24)25)12(2)19(26-20)14-4-8-15(21)9-5-14/h4-11H,3H2,1-2H3,(H2,22,24,25)
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| Chemical Name |
4-(5-(4-chlorophenyl)-4-methyl-2-propionylthiophen-3-yl)benzenesulfonamide
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| Synonyms |
nAChR agonist 1
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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 : ~125 mg/mL (~297.66 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.95 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3813 mL | 11.9065 mL | 23.8129 mL | |
| 5 mM | 0.4763 mL | 2.3813 mL | 4.7626 mL | |
| 10 mM | 0.2381 mL | 1.1906 mL | 2.3813 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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