| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
mAChR M4 (muscarinic acetylcholine receptor M4).
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|---|---|
| ln Vitro |
VU0467154 is a muscarinic acetylcholine receptor (mAChR) positive allosteric modulator that has pEC50s of 7.75, 6.2, and 6.2 for rat, human, and cynomolgus monkey (cyno) M4 receptors, respectively. It can greatly increase the responsiveness to ACh. 6. In rats and humans, VU0467154 did not increase ACh responses in M1, M2, M3, or M5 [1].
VU0467154 is a positive allosteric modulator of M4 mAChR that robustly potentiates the response to ACh with pEC50 values of 7.75, 6.2, and 6 for rat, human, and cynomolgus monkey M4 receptors, respectively. |
| ln Vivo |
Rats' amphetamine-induced hyperlocomotion is reversed by VU0467154 (1–56.6 mg/kg, oral or intraperitoneal injection). In wild-type mice, VU0467154 (0.3-30 mg/kg, ip) reverses the hyperlocomotion caused by amphetamine and MK-801, but not in M4 KO mice. In wild-type mice, VU0467154 alone also improves the learning of context- and cue-mediated fear conditioning [1].
In vivo, VU0467154 produces a robust dose-dependent reversal of MK-801-induced hyperlocomotion and deficits in preclinical models of associative learning and memory functions in wild-type mice. |
| Enzyme Assay |
The compound's modulation of M4 receptor is assessed in cell-free membrane preparations using radioligand binding assays to confirm binding to the M4 receptor and determine its mode of allosteric modulation.
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| Cell Assay |
VU0467154 is evaluated in cell-based functional assays using CHO cells expressing rat, human, or cynomolgus monkey M4 receptors. Calcium mobilization or other second messenger assays measure the compound's ability to potentiate acetylcholine-induced responses, with EC50 values determined.
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| Animal Protocol |
In vivo studies are conducted in wild-type mice to assess the compound's ability to reverse MK-801-induced hyperlocomotion and deficits in associative learning and memory functions, including the touchscreen pairwise visual discrimination task.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is available for VU0467154. As a brain-penetrant compound, it is expected to have suitable PK properties for CNS studies, but specific parameters have not been reported.
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| Toxicity/Toxicokinetics |
No detailed toxicological data is available for this compound. As a research-grade chemical probe, standard preclinical toxicity assessments have not been published.
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| References | |
| Additional Infomation |
VU0467154 is a potent and selective M4 mAChR positive allosteric modulator that exhibits robust antipsychotic-like and cognitive enhancing activity in rodents. Selective M4 PAMs could provide a therapeutic strategy for the treatment of Huntington's disease, schizophrenia, and other neuropsychiatric disorders. It has not advanced to clinical trials and is not FDA-approved.
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| Molecular Formula |
C17H15F3N4O3S2
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|---|---|
| Molecular Weight |
444.451211214066
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| Exact Mass |
444.054
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| CAS # |
1451993-15-9
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| Related CAS # |
1451993-15-9;
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| PubChem CID |
73774630
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.166
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
708
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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)S(=O)(=O)C(F)(F)F)N)C
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| InChi Key |
UDSFKIFLJPECRN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H15F3N4O3S2/c1-8-9(2)23-24-16-12(8)13(21)14(28-16)15(25)22-7-10-3-5-11(6-4-10)29(26,27)17(18,19)20/h3-6H,7,21H2,1-2H3,(H,22,25)
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| Chemical Name |
5-amino-3,4-dimethyl-N-[[4-(trifluoromethylsulfonyl)phenyl]methyl]thieno[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 : ~13.89 mg/mL (~31.25 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 1.39 mg/mL (3.13 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 13.9 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2500 mL | 11.2499 mL | 22.4997 mL | |
| 5 mM | 0.4500 mL | 2.2500 mL | 4.4999 mL | |
| 10 mM | 0.2250 mL | 1.1250 mL | 2.2500 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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