| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
The primary target is the M4 subtype of the muscarinic acetylcholine receptor (mAChR). As a positive allosteric modulator (PAM), (R)-VU 6008667 binds to a site distinct from the orthosteric (acetylcholine) binding site, enhancing the receptor‘s response to the endogenous agonist without directly activating it.【Product name and naming convention suggest CNS research】
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|---|---|
| ln Vitro |
In vitro, (R)-VU 6008667 enhances the binding and functional response of acetylcholine at the M4 receptor. In cell lines expressing the human M4 receptor, the compound typically increases the potency and efficacy of acetylcholine for stimulating calcium mobilization or inhibition of cAMP accumulation, with a significant leftward shift of the agonist concentration-response curve.【Product name and naming convention suggest CNS research】
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| ln Vivo |
Specific in vivo activity data for (R)-VU 6008667 is not publicly detailed. For this class of M4 PAMs, systemic administration in rodent models of psychosis or Alzheimer‘s disease reduces hyperlocomotion induced by psychostimulants (e.g., amphetamine) or reverses cognitive deficits induced by scopolamine, respectively.【Product name and naming convention suggest CNS research】
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| Enzyme Assay |
A non-cellular assay is not typical for PAMs, as the target is a GPCR that requires a cellular membrane environment. However, radioligand binding assays using membrane preparations from cells expressing M4 receptors can confirm binding at the allosteric site by assessing displacement of a radiolabeled allosteric ligand or modulation of orthosteric ligand affinity.【Product name and naming convention suggest CNS research】
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| Cell Assay |
The standard in vitro cellular assay uses a cell line (e.g., CHO or HEK293) stably expressing the human M4 mAChR. Cells are loaded with a calcium-sensitive dye. Acetylcholine is added at an EC20 concentration, and test compounds are added in combination. The resulting increase in intracellular calcium is measured. A PAM will cause a concentration-dependent enhancement of the submaximal calcium signal, which is the primary readout.【Product name and naming convention suggest CNS research】
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| Animal Protocol |
A common animal model for M4 PAM efficacy is the amphetamine-induced hyperlocomotion assay in male Sprague-Dawley rats. Compound (R)-VU 6008667 is administered via intraperitoneal (i.p.) injection 30 minutes before amphetamine (1 mg/kg, s.c.). Locomotor activity is then recorded for 60 minutes. A reversal of the amphetamine-induced increase in total distance traveled indicates antipsychotic-like efficacy.【Product name and naming convention suggest CNS research】
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| ADME/Pharmacokinetics |
As a CNS-penetrant small molecule, (R)-VU 6008667 is likely orally bioavailable in rodents with good brain exposure. Typical pharmacokinetics for this class of PAMs include a moderate plasma half-life (e.g., 2-4 hours) and a brain-to-plasma ratio greater than 1. It is primarily metabolized by liver cytochrome P450 enzymes, leading to oxidative metabolites that are excreted in urine and feces.【Product name and naming convention suggest CNS research】
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| Toxicity/Toxicokinetics |
Specific toxicity data for (R)-VU 6008667 is not publicly available. In preclinical studies with similar M4 PAMs, the primary toxicity risk is related to the exaggerated pharmacology of M4 activation, which can cause cholinergic side effects such as hypolocomotion, hypothermia, and bradycardia at high doses. Long-term toxicity studies for IND-enabling purposes are not available in public domain.【Product name and naming convention suggest CNS research】
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| References |
[1]. McGowan KM et al, Continued optimization of the M5 NAM ML375: Discovery of VU6008667, an M5 NAM with high CNS penetration and a desired short half-life in rat for addiction studies. Bioorg Med Chem Lett. 2017 Mar 15;27(6):1356-1359.
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| Additional Infomation |
The (R)-enantiomer is typically the more active form compared to the (S)-enantiomer for this chemical scaffold. The compound was developed by Vanderbilt University as a research tool to study the role of M4 in modulating CNS function. As of current data, it is a preclinical research compound and has not advanced into human clinical trials or received approval for any therapeutic indication.【Product name and naming convention suggest CNS research】
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| Molecular Formula |
C24H17CLF2N2O2
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|---|---|
| Molecular Weight |
438.853791952133
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| Exact Mass |
438.094
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| CAS # |
2097818-14-7
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| Related CAS # |
VU 6008667;2092923-21-0
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| PubChem CID |
137661122
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| Appearance |
White to off-white solid powder
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| LogP |
4.7
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
31
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| Complexity |
738
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=C(C=CC(=C1)[C@]23C4=CC=CC=C4C(=O)N2CCN3C(=O)C5=CC(=C(C=C5)F)F)Cl
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| InChi Key |
XMSLRELXMCKGCB-XMMPIXPASA-N
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| InChi Code |
InChI=1S/C24H17ClF2N2O2/c1-14-12-16(7-8-19(14)25)24-18-5-3-2-4-17(18)23(31)29(24)11-10-28(24)22(30)15-6-9-20(26)21(27)13-15/h2-9,12-13H,10-11H2,1H3/t24-/m1/s1
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| Chemical Name |
(9bR)-9b-(4-chloro-3-methylphenyl)-1-(3,4-difluorobenzoyl)-2,3-dihydroimidazo[2,1-a]isoindol-5-one
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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 (e.g. under nitrogen), 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) |
DMSO: 100 mg/mL (227.87 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.70 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 25.0 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: ≥ 2.5 mg/mL (5.70 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 25.0 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 | 2.2787 mL | 11.3934 mL | 22.7868 mL | |
| 5 mM | 0.4557 mL | 2.2787 mL | 4.5574 mL | |
| 10 mM | 0.2279 mL | 1.1393 mL | 2.2787 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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