| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
The primary target of VU 6008667 is the M5 muscarinic acetylcholine receptor (mAChR), a G protein-coupled receptor predominantly expressed in the central nervous system. It acts as a negative allosteric modulator (NAM), meaning it binds to a site distinct from the orthosteric binding site and reduces the receptor's response to acetylcholine without directly competing with the endogenous ligand. This allosteric modulation provides selectivity for the M5 subtype over other mAChR subtypes. The M5 receptor is involved in various neurological processes, including reward, addiction, and cognition, making it a target of interest for studying neurological and psychiatric disorders.
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| ln Vitro |
In vitro studies have demonstrated that VU 6008667 is a potent and selective NAM of the M5 receptor with IC₅0 values of 1.2 microM for the human M5 receptor and 1.6 microM for the rat M5 receptor. It exhibits selectivity for M5 over other muscarinic receptor subtypes. The compound's activity is typically assessed using cell-based functional assays such as calcium mobilization or IP1 accumulation assays to measure receptor-mediated signaling. VU 6008667 has been shown to effectively reduce M5 receptor activity in vitro, making it a useful tool for studying the physiological and pathological roles of M5 in various cell types and tissues.
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| ln Vivo |
A half-life of 2.3 hours (t1/2 = 2.3 hr) is shown by the volume (Vss = 7.4 L/kg) of VU 6008667 (1 mg/kg or 3 mg/kg, with lesser deposition) and the above clearance rate.
In vivo studies of VU 6008667 are primarily focused on its effects in animal models of neurological and metabolic disorders. The compound's high CNS penetration makes it suitable for central administration in rodent models. It is used in neuroscience and metabolic research to study amino acid transport, nutrient sensing, and their roles in brain function and disease. VU 6008667 provides a valuable tool for exploring SNAT2's physiological and pathological roles in cancer metabolism, neurodegeneration, and metabolic disorders. Further in vivo studies are needed to fully characterize its pharmacokinetic and pharmacodynamic profiles. |
| Enzyme Assay |
For in vitro enzyme/receptor binding assays, VU 6008667 can be evaluated using radioligand binding studies with membranes expressing the human or rat M5 receptor. Competition binding experiments using a labeled muscarinic antagonist can determine the compound's affinity for the allosteric binding site. Surface plasmon resonance (SPR) or other biophysical techniques may be employed to study the binding kinetics. Functional allosteric modulation can be assessed using calcium flux assays or electrophysiological recordings in cells expressing the M5 receptor. Dose-response curves are generated to determine IC₅0 values for inhibition of acetylcholine-induced responses.
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| Cell Assay |
For in vitro cellular experiments, VU 6008667 is typically tested in cell lines expressing the human or rat M5 receptor, such as CHO or HEK293 cells stably transfected with the receptor. Cells are cultured in appropriate media and treated with various concentrations of the compound (typically ranging from nanomolar to micromolar) in the presence of acetylcholine or other agonists. Receptor activity is measured using calcium-sensitive dyes, IP1 accumulation assays, or other functional readouts. The compound's effects on cell signaling pathways can be further investigated using phospho-protein analysis or gene expression profiling. Cytotoxicity and cell viability should be monitored to ensure that observed effects are receptor-mediated.
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| Animal Protocol |
Animal/Disease Models: RAT (PK Study)[1]
Doses: 1 mg/kg; , CLp = 82 mL/min/kg, showing porous bioavailability of 17% (17%F)[1]. 3 mg/kg Route of Administration: Oral Administration Experimental Results: Desirably short half-life (t1/2= 2.3 hrs (hrs (hours))) and moderate oral bioavailability (17% F) in rats. For in vivo animal experiments, VU 6008667 is typically administered to rodents via intraperitoneal (IP) or oral gavage routes to assess its effects on M5 receptor-mediated behaviors and physiological functions. The compound's high CNS penetration allows for evaluation of central effects following systemic administration. Doses may range from 1 to 30 mg/kg depending on the study design. Behavioral tests such as locomotor activity, cognitive assays, or models of addiction can be used to assess the functional consequences of M5 modulation. Tissue distribution and receptor occupancy studies may be performed to correlate drug exposure with pharmacological effects. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of VU 6008667 include high CNS penetration, suggesting favorable blood-brain barrier permeability. The compound is likely to have moderate oral bioavailability and a reasonable half-life for in vivo studies. Its molecular weight of 438.85 g/mol and lipophilic characteristics (due to the presence of chloro, fluoro, and methyl groups) are consistent with CNS-active compounds. Detailed pharmacokinetic parameters such as Cₘₐₓ, Tₘₐₓ, AUC, and half-life would need to be determined through comprehensive PK studies. The compound's metabolism and clearance pathways have not been fully characterized in the public literature.
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| Toxicity/Toxicokinetics |
Toxicological data for VU 6008667 are limited, as the compound is primarily a research tool. Standard toxicology screening would include assessment of cytotoxicity in relevant cell lines, hERG channel inhibition to evaluate cardiac safety, and preliminary in vivo toxicity in rodent models. The compound's selectivity for M5 over other mAChR subtypes may reduce the risk of off-target effects associated with pan-muscarinic modulation. As with all research chemicals, appropriate safety precautions should be taken when handling VU 6008667, including the use of personal protective equipment and adherence to institutional safety guidelines for handling potentially hazardous compounds.
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| References | |
| Additional Infomation |
VU 6008667 is a research compound primarily used in neuroscience and metabolic research to study the M5 muscarinic receptor. No clinical trials or regulatory approvals have been reported for this compound as a therapeutic agent. It is available from various chemical suppliers for research purposes only. The compound serves as a valuable tool for exploring SNAT2's physiological and pathological roles in cancer metabolism, neurodegeneration, and metabolic disorders. Its high CNS penetration makes it particularly useful for studying central nervous system functions of the M5 receptor. Further research may elucidate its potential therapeutic applications.
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| Molecular Formula |
C29H34CL2FN3O3
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|---|---|
| Molecular Weight |
562.502969264984
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| Exact Mass |
438.094
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| CAS # |
2092923-21-0
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| Related CAS # |
(R)-VU 6008667;2097818-14-7
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| PubChem CID |
134824563
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| Appearance |
Light yellow to yellow 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 |
ClC1C=CC2=C(C=1)NC([C@@]12[C@@H](C2C=CC=C(C=2F)Cl)[C@H](C(NC2CCC(CC2)O)=O)N[C@H]1CC(C)(C)C)=O
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| InChi Key |
XMSLRELXMCKGCB-DEOSSOPVSA-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-/m0/s1
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| Chemical Name |
(9bS)-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 | 1.7778 mL | 8.8889 mL | 17.7778 mL | |
| 5 mM | 0.3556 mL | 1.7778 mL | 3.5556 mL | |
| 10 mM | 0.1778 mL | 0.8889 mL | 1.7778 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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