| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
VU0467485 targets the muscarinic acetylcholine receptor 4 (M4), a G protein-coupled receptor that is highly expressed in the brain and is involved in the regulation of dopamine release and cognitive function. As a PAM, it enhances the activity of acetylcholine at the M4 receptor, potentiating its physiological effects.
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| ln Vitro |
In vitro, VU0467485 is a potent and selective M4 PAM. It potentiates the activity of acetylcholine at the M4 receptor with EC50 values of 26.6 nM at the rat receptor and 78.8 nM at the human receptor. It shows selectivity for M4 over human and rat M1, M2, M3, and M5 receptors.
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| ln Vivo |
Rat models of amphetamine-induced hyperlocomotion (AHL) have shown antipsychotic-like action in response to VU0467485 (1–10 mg/kg; oral) [1]. Cmax, AUCo-inf, and elimination t1/2 of VU0467485 (3 mg/kg; oral) were 1.2 μM, 3.8 μM·h, and 4.2 hours, respectively [1].
In vivo, VU0467485 demonstrates antipsychotic-like activity in rat models of amphetamine-induced hyperlocomotion (AHL) at doses of 1-10 mg/kg via oral administration. The compound has moderate to high CNS penetration. In a pharmacokinetic study at 3 mg/kg (p.o.), it exhibited a Cmax of 1.2 μM, an AUC0-inf of 3.8 μM·h, and an elimination half-life (t1/2) of 4.2 hours. |
| Enzyme Assay |
In vitro receptor binding assays are not typically performed for PAMs as traditional binding assays; instead, functional assays are used to measure their activity. These assays assess the compound's ability to potentiate the effect of a sub-maximal concentration of acetylcholine at the M4 receptor.
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| Cell Assay |
In vitro cellular assays are performed using cell lines expressing the human or rat M4 receptor. Cells are treated with a sub-maximal concentration of acetylcholine in the presence of increasing concentrations of VU0467485, and receptor activation is measured. The EC50 values of 26.6 nM (rat) and 78.8 nM (human) are calculated from these curves.
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| Animal Protocol |
Animal/Disease Models: Sprague Dawley rat (amphetamine-induced hyperexercise rat model) [1]
Doses: 1, 3, 10 mg/kg Route of Administration: Oral Experimental Results: Dose-dependent reversal of AHL. Animal/Disease Models: Male sprague Dawley rat[1] Doses: Orally (pharmacokinetic/PK/PK analysis) Doses: 3 mg/kg Experimental Results: Cmax, AUCo-inf and elimination t1/2 were 1.2 μM and 3.8 μM·h respectively and 4.2 hrs (hrs (hours)). In vivo animal experiments are conducted in rat models of amphetamine-induced hyperlocomotion (AHL). VU0467485 is administered orally at doses of 1, 3, and 10 mg/kg, resulting in a dose-dependent reversal of hyperlocomotion. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies in male Sprague-Dawley rats after a single 3 mg/kg oral dose reveal a Cmax of 1.2 μM, AUC0-inf of 3.8 μM·h, and elimination t1/2 of 4.2 hours.
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| Toxicity/Toxicokinetics |
Toxicological data is limited, but its antipsychotic-like activity and safety profile have been evaluated in preclinical models.
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| References | |
| Additional Infomation |
VU0467485 is a research compound and is not approved for clinical use. It has been advanced as a preclinical candidate for neuropsychiatric disorders such as schizophrenia based on its robust efficacy in behavioral models.
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| Molecular Formula |
C17H17FN4O2S
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|---|---|
| Molecular Weight |
360.4059
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| Exact Mass |
360.105
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| CAS # |
1451994-10-7
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| PubChem CID |
89777239
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.660
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| LogP |
3.11
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
486
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(N=NC2=C1C(=C(S2)C(=O)NCC3=CC(=C(C=C3)OC)F)N)C
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| InChi Key |
VFNHDIWHQGVWLL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H17FN4O2S/c1-8-9(2)21-22-17-13(8)14(19)15(25-17)16(23)20-7-10-4-5-12(24-3)11(18)6-10/h4-6H,7,19H2,1-3H3,(H,20,23)
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| Chemical Name |
5-amino-N-[(3-fluoro-4-methoxyphenyl)methyl]-3,4-dimethylthieno[2,3-c]pyridazine-6-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 : ~20 mg/mL (~55.49 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 | 2.7746 mL | 13.8731 mL | 27.7462 mL | |
| 5 mM | 0.5549 mL | 2.7746 mL | 5.5492 mL | |
| 10 mM | 0.2775 mL | 1.3873 mL | 2.7746 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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