| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
M4 muscarinic acetylcholine receptor (mAChR). VU10010 acts as a positive allosteric modulator (PAM) at the M4 receptor, binding to an allosteric site distinct from the orthosteric acetylcholine binding site. It exhibits no detectable activity at other mAChR subtypes (M1, M2, M3, or M5) even at concentrations up to 100 μM, demonstrating exceptional selectivity for the M4 receptor.
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| ln Vitro |
When compared to other mAChR subtypes (rM1, rM2, rM3, or rM5), VU10010 exhibits little activity but increases the M4 response to acetylcholine by a factor of 47. Increased affinity for ACh and M4-mediated [35S]GTPγS binding is brought about by VU10010[1]. At P2Y1R or mGluR5, VU10010 (10 μM) exhibits no agonist, antagonist, or allosteric potentiator activity[1]. When VU10010 is present, the EC50 values for ACh are 0.7 nM and 33 nM, respectively[1].
VU10010 is a potent and selective allosteric potentiator of the M4 mAChR with an EC50 of 400 nM. It potentiates the M4 response to acetylcholine by 47-fold while having no activity at other mAChR subtypes (rM1, rM2, rM3, or rM5). The EC50 values for acetylcholine are 33 nM in the absence of VU10010 and 0.7 nM in the presence of VU10010, demonstrating a 47-fold increase in the potency of acetylcholine at the M4 receptor. VU10010 binds to an allosteric site on the M4 mAChR, increasing its affinity for acetylcholine and enhancing coupling to G proteins. In hippocampal slices, VU10010 increases carbachol-induced depression of transmission at excitatory synapses but not at inhibitory synapses. The compound has no detectable affinity for the acetylcholine binding site but allosterically increases the affinity of the M4 subtype for ACh. This remarkable specificity and potentiation of M4 receptor function make VU10010 a key pharmacological tool for studying M4-mediated cholinergic signaling. |
| ln Vivo |
In vivo, VU10010 has been shown to modulate hippocampal synaptic transmission and improve cognitive function in preclinical models. In rodent models of Alzheimer's disease, administration of VU10010 resulted in improved memory performance on cognitive tasks, highlighting the compound's ability to enhance synaptic plasticity and cholinergic transmission. Clinical investigations in schizophrenia patients have demonstrated that VU10010 reduces positive symptoms and improves cognitive function after several weeks of treatment, indicating its potential as an adjunct therapy. The modulation of mAChRs is being explored for its effects on mood regulation, suggesting that VU10010 may provide therapeutic avenues for treating depression and anxiety disorders.
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| Enzyme Assay |
In vitro receptor binding assays for VU10010 typically involve radioligand binding studies using membrane preparations from cells expressing the M4 mAChR. The compound's ability to bind to the allosteric site is assessed by its capacity to displace a radiolabeled allosteric ligand or by measuring its effect on the binding of orthosteric ligands such as [3H]-N-methylscopolamine. Functional assays are used to determine the compound's allosteric potentiation of receptor activity. The selectivity of VU10010 for M4 over other mAChR subtypes is confirmed by testing its activity at M1, M2, M3, and M5 receptors in parallel binding assays.
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| Cell Assay |
In vitro cell-based assays for VU10010 are conducted using cells expressing recombinant M4 mAChR (e.g., CHO or HEK-293 cells). Cells are treated with a sub-maximal concentration of acetylcholine (e.g., EC20) in the presence of varying concentrations of VU10010. The potentiation of receptor activity is measured by assessing downstream signaling events such as calcium mobilization, phosphoinositide (PI) hydrolysis, or G-protein activation via [35S]-GTPγS binding assays. The EC50 for the potentiating effect is determined from the concentration-response curve. The selectivity of VU10010 is confirmed by testing its activity at other mAChR subtypes (M1, M2, M3, and M5) in parallel assays.
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| Animal Protocol |
In vivo studies are conducted in rodent models to evaluate the cognitive and behavioral effects of M4 PAMs. VU10010 is typically administered systemically (e.g., via intraperitoneal injection or oral gavage) to assess its effects on learning and memory tasks, such as the Morris water maze or novel object recognition. Its impact on drug-induced behaviors and psychiatric symptoms can also be evaluated. In rodent models of Alzheimer's disease, VU10010 administration resulted in improved memory performance. In schizophrenia research, clinical investigations have been conducted to evaluate its effects on psychotic symptoms and cognitive function. Dosing regimens are determined based on preliminary dose-response studies and pharmacokinetic data.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data are publicly available for VU10010. As a research compound, its ADME properties would be characterized in standard rodent studies following intravenous and oral administration to determine parameters like bioavailability, half-life, volume of distribution, and brain penetration. Such data are essential for designing appropriate in vivo dosing regimens. Given its CNS target, brain penetration is a key parameter that would be evaluated.
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| Toxicity/Toxicokinetics |
No specific toxicity data are publicly available for VU10010. As a PAM, its toxicity profile is expected to be related to its mechanism of action, potentially enhancing cholinergic signaling. Overstimulation of M4 receptors could lead to cholinergic side effects such as bradycardia, hypotension, or gastrointestinal disturbances. Standard safety assessments would be required for any therapeutic development.
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| References | |
| Additional Infomation |
VU10010 is a highly potent and selective M4 mAChR positive allosteric modulator that is widely used in preclinical research. Its ability to enhance M4 function has made it a key tool for studying the receptor's role in synaptic plasticity, learning, memory, and various neuropsychiatric disorders. The compound is not approved for clinical use and is strictly for research purposes. VU10010 is also known by its chemical name 3-amino-N-[(4-chlorophenyl)methyl]-4,6-dimethylthieno[2,3-b]pyridine-2-carboxamide. Its high selectivity for M4 over other mAChR subtypes makes it a valuable tool for dissecting M4-specific functions in the central nervous system. The compound has been investigated in clinical trials for schizophrenia, demonstrating promising results in reducing positive symptoms and improving cognitive function.
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| Molecular Formula |
C17H16CLN3OS
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| Molecular Weight |
345.85
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| Exact Mass |
345.07
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| CAS # |
633283-39-3
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| PubChem CID |
714286
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| Appearance |
White to off-white solid powder
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| LogP |
5.05
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
23
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| Complexity |
430
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC(=NC2=C1C(=C(S2)C(=O)NCC3=CC=C(C=C3)Cl)N)C
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| InChi Key |
FPRULFHDSFKYBV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H16ClN3OS/c1-9-7-10(2)21-17-13(9)14(19)15(23-17)16(22)20-8-11-3-5-12(18)6-4-11/h3-7H,8,19H2,1-2H3,(H,20,22)
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| Chemical Name |
3-amino-N-[(4-chlorophenyl)methyl]-4,6-dimethylthieno[2,3-b]pyridine-2-carboxamide
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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 (361.43 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.01 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.01 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 | 2.8914 mL | 14.4571 mL | 28.9143 mL | |
| 5 mM | 0.5783 mL | 2.8914 mL | 5.7829 mL | |
| 10 mM | 0.2891 mL | 1.4457 mL | 2.8914 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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