| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) is a homopentameric ligand-gated ion channel that is highly expressed in the hippocampus and cortex. Upon activation by acetylcholine, it facilitates rapid calcium influx, leading to the release of neurotransmitters like glutamate and GABA. This process is crucial for synaptic plasticity and cognitive function. (S)-VQW-765 acts as a partial agonist, binding to and activating the receptor but with lower intrinsic efficacy than the full agonist acetylcholine.
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| ln Vitro |
As a partial agonist, (S)-VQW-765 activates the alpha7 nAChR. In standard electrophysiological assays, the compound induces inward currents through the receptor in a concentration-dependent manner. Compared to the full agonist, it produces sub-maximal activation. This partial agonist profile might be advantageous in a therapeutic setting to avoid receptor desensitization. The S-enantiomer is the active form responsible for the pharmacological activity.
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| ln Vivo |
In vivo, (S)-VQW-765 (AQW-051) is designed for oral administration to treat cognitive deficits. Preclinical studies in animal models (such as rodents and non-human primates) have been conducted to assess its pro-cognitive effects. In models of cognitive impairment, including those induced by cholinergic antagonists or in transgenic Alzheimer's models, alpha7 nAChR partial agonists like AQW-051 have shown the ability to improve attention, working memory, and learning performance, though specific data for this enantiomer is primarily from in vitro studies.
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| Enzyme Assay |
The binding affinity of (S)-VQW-765 is determined using a radioligand binding assay. Membrane preparations from HEK-293 cells expressing the human alpha7 nAChR are incubated with the selective radioligand [125I]-alpha-bungarotoxin or [3H]-MLA (methyllycaconitine). Varying concentrations of (S)-VQW-765 are added to compete with the radioligand. After incubation and filtration to separate bound ligand, the Ki is calculated from the IC50.
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| Cell Assay |
The functional activity of the compound is measured using calcium flux assays. Cells stably expressing the human alpha7 nAChR (often GH4C1 cells) are loaded with a calcium-sensitive dye like Fluo-4-AM. Upon addition of (S)-VQW-765, the change in fluorescence (ex/em 490/525 nm) is measured in a plate reader. As a partial agonist, the maximal response (Emax) is compared to the full agonist acetylcholine to determine its intrinsic efficacy.
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| Animal Protocol |
For in vivo efficacy studies, (S)-VQW-765 would be administered orally to rats or mice. Behavioral models used to evaluate pro-cognitive effects include the novel object recognition (NOR) test to assess memory, the five-choice serial reaction time task (5-CSRTT) to measure attention, and the Morris water maze (MWM) to assess spatial learning. Active treatment groups are compared to a scopolamine-induced amnesia model or a vehicle control group.
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| ADME/Pharmacokinetics |
(S)-VQW-765 is orally active. The compound is generally formulated as a suspension in 0.5% methylcellulose or a solution in saline for oral gavage in preclinical studies. It has favorable drug-like properties, including sufficient metabolic stability and good brain penetration to reach the target receptors in the central nervous system. Detailed PK parameters such as half-life and Cmax are not publicly available.
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| Toxicity/Toxicokinetics |
Toxicological data for this specific compound is limited. alpha7 nAChR agonists and partial agonists as a class are generally considered to have a manageable safety profile. Due to the expression of alpha7 receptors in the hippocampus, potential side effects are primarily CNS-related and could include mild headache, dizziness, or gastrointestinal issues at high doses. No severe systemic toxicity or genotoxicity has been reported in preclinical studies for this class.
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| References | |
| Additional Infomation |
(S)-VQW-765 (also known as (S)-AQW-051) is a research-grade chemical tool for studying the alpha7 nAChR. It is not a marketed drug nor FDA-approved. While AQW-051 was progressed into early clinical trials by Novartis (e.g., for schizophrenia), its development may have been deprioritized. This research compound remains valuable for exploring the role of alpha7 nAChR partial agonism in cognition. AQW051 was discontinued after Phase I for Alzheimer's Disease and Phase II for Schizophrenia.
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| Molecular Formula |
C19H22N2O
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| Molecular Weight |
294.39
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| Related CAS # |
VQW-765;669770-29-0
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| Appearance |
White to off-white solid powder
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 3.3969 mL | 16.9843 mL | 33.9685 mL | |
| 5 mM | 0.6794 mL | 3.3969 mL | 6.7937 mL | |
| 10 mM | 0.3397 mL | 1.6984 mL | 3.3969 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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