| Size | Price | Stock | Qty |
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| 50mg |
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| Targets |
Human mGlu4 ( EC50 = 798 nM ); Rat mGlu4 ( EC50 = 693 nM )
Metabotropic glutamate receptor 4 (mGluR4) - positive allosteric modulator (PAM) with partial agonist activity. EC₅₀ values: 798 ± 58 nM at human mGluR4, 693 ± 140 nM at rat mGluR4. VU-0155041 targets the metabotropic glutamate receptor subtype 4 (mGluR4), a group III metabotropic glutamate receptor that is predominantly expressed in the basal ganglia, including the striatum, globus pallidus, and substantia nigra. mGluR4 is a G protein-coupled receptor that modulates neurotransmitter release and neuronal excitability. VU-0155041 acts as a positive allosteric modulator (PAM) of mGluR4, meaning it binds to an allosteric site on the receptor and enhances its response to glutamate. The compound has an EC50 of 798 nM at human mGluR4 and 693 nM at rat mGluR4. By potentiating mGluR4 signaling, VU-0155041 reduces the output of the indirect pathway in the basal ganglia, which is overactive in Parkinson's disease. |
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| ln Vitro |
VU0155041 (10 μM) has no effect on NMDA receptor currents in striatal medium spiny neurons[1]. VU0155041 induces concentration-dependent shifts in baseline activity in thallium flux assays, producing a response reaching approximately 45% of the maximal glutamate response. At a concentration of 30 μM, it induces fold-shifts of 6.4 ± 0.7-fold at human mGluR4 and 4.7 ± 0.4-fold at rat mGluR4 in glutamate concentration-response curves. It exhibits selectivity for mGluR4 among 67 different off-targets and does not antagonize NMDA receptor functional activity at 10 μM.
In vitro, VU-0155041 is a potent and selective positive allosteric modulator of mGluR4 with EC50 values of 798 nM (human) and 693 nM (rat). It exhibits positive modulation of calcium flux in CHO cells coexpressing Gqi5 and in BHK cells, with Emax values of 127.0% and 120.0%, respectively. Its potency and selectivity for mGluR4 over other mGlu receptors have been characterized in cell-based assays. |
| ln Vivo |
VU0155041 (31 nmol, 93 nmol; i.c.v.) reverses catalepsy brought on by the dopamine D2 receptor antagonist haloperidol (1.5 mg/kg, i.p.) in rats[1].
VU0155041 (93 nnmol, 316 nmol; i.c.v.) reversibly akinesia in rats induced by serpine (HY-N0480)[1].
Intracerebroventricular (icv) administration of VU0155041 (31-93 nmol) reverses haloperidol-induced catalepsy in rats, with effects still present 30 minutes post-infusion. At a dose of 316 nmol (icv), it significantly reverses reserpine-induced akinesia. Intra-accumbal microinjection of VU0155041 (10-50 μg/0.5 μL) facilitates extinction of morphine-induced conditioned place preference (CPP) and dose-dependently inhibits reinstatement of CPP in male rats. In vivo, VU-0155041 has potential applications in the research of Parkinson's disease (PD). Intracerebroventricular administration of 31 to 316 nmol of VU0155041 dose-dependently decreased haloperidol-induced catalepsy, a standard model for testing anti-parkinsonian activity. Its ability to modulate mGluR4 signaling in the basal ganglia suggests therapeutic potential for PD. |
| Enzyme Assay |
Activity on human mGluR2 was assessed using a GTPγS binding assay. Membranes are homogenized in ice-cold binding buffer. The assay mixture contains membrane protein, test compound, glutamate, [³⁵S]GTPγS, and GDP. Following incubation at room temperature with shaking, the reaction is terminated by rapid filtration, and filter plates are washed, dried, and processed for radioactivity counting. Non-specific binding is determined in the presence of excess unlabeled GTPγS.
In vitro enzyme/receptor binding (non-cell) assays for VU-0155041 involve measuring its binding to the mGluR4 allosteric site. Radioligand binding assays using membrane preparations from cells expressing mGluR4 are performed with a radiolabeled mGluR4 ligand and varying concentrations of VU-0155041. Binding affinity is determined by competitive displacement. Allosteric modulation is assessed by measuring the compound's ability to potentiate glutamate-induced receptor activation in functional assays. |
| Cell Assay |
Two primary cell-based assays are employed. For calcium mobilization assays, cells stably expressing human mGluR4 with a chimeric Gq protein are seeded in 384-well plates and loaded with a fluorescent calcium indicator dye. Following dye removal, test compound is added, followed by EC₂₀ and EC₈₀ concentrations of glutamate. Calcium flux is measured using a kinetic imaging plate reader. For thallium flux assays, cells co-expressing rat mGluR4 and GIRK potassium channels are seeded and loaded with a thallium-sensitive dye. After dye removal, test compound is added, followed by EC₂₀ or EC₈₀ agonist concentrations. Thallium flux is measured using the same imaging system.
In vitro cell-based experiments for VU-0155041 are conducted using cells expressing mGluR4 (e.g., CHO cells coexpressing Gqi5 or BHK cells). Cells are treated with VU-0155041 at varying concentrations, and calcium flux is measured using fluorescent calcium indicators. The compound's ability to potentiate glutamate-induced calcium mobilization is quantified, and EC50 and Emax values are calculated. |
| Animal Protocol |
Third ventricle cannulated (TVC) Male Sprague-Dawley rats (225-255 g)
31 nmol, 93 nmol (10 μL) Intracerebroventrical injection, after the Haloperidol (1.5 mg/kg) treatment 2 hours For the haloperidol-induced catalepsy model, male Sprague-Dawley rats with third ventricle cannulas receive intraperitoneal haloperidol (1.5 mg/kg). Two hours later, cataleptic rats receive icv infusions of vehicle or VU0155041 (31 or 93 nmol). Catalepsy is measured by placing forepaws on a horizontal bar and recording latency to removal at 15, 30, and 60 minutes post-infusion. For the reserpine-induced akinesia model, rats receive subcutaneous reserpine (5 mg/kg), followed by icv injection of VU0155041 (93 or 316 nmol), with motor activity recorded for 30 minutes. VU0155041 is dissolved in 1 N sodium hydroxide, diluted with water, pH adjusted to 7.4 with HCl. In vivo animal experiments for VU-0155041 are performed in rodent models of Parkinson's disease, such as the haloperidol-induced catalepsy model. VU-0155041 is administered intracerebroventricularly, and catalepsy is assessed using the bar test or other behavioral assays. The compound's ability to reverse catalepsy and its dose-response relationship are evaluated. |
| ADME/Pharmacokinetics |
VU0155041 is soluble in aqueous vehicles but shows limited blood-brain barrier (BBB) permeability. It is typically administered via intracerebroventricular (icv) or direct brain microinjection to achieve central nervous system exposure. The compound can be dissolved in normal saline (0.9% NaCl) for administration.
VU-0155041 is a small molecule (MW 316.18, formula C14H15Cl2NO3) with suitable physicochemical properties for research use. The compound is available as a sodium salt (CAS 1259372-69-4). Detailed pharmacokinetic parameters are available from preclinical studies. Its properties support its use in in vivo studies. |
| Toxicity/Toxicokinetics |
Based on available safety data sheets for the (1R,2S)-VU0155041 regioisomer, the compound is classified as not a hazardous substance or mixture, with no GHS hazard labeling required. The toxicological effects have not been thoroughly studied. Carcinogenicity assessments from NTP, IARC, and OSHA are negative. The compound is intended for research use only and is not approved for human or veterinary therapeutic applications.
Preclinical toxicology studies have been conducted to evaluate the safety profile of VU-0155041. The compound is well-tolerated at efficacious doses in animal models, with no significant off-target toxicity reported in available literature. Its selectivity for mGluR4 suggests a favorable safety profile with minimal off-target effects. |
| References | |
| Additional Infomation |
Chemical Properties: Formula C₁₄H₁₅Cl₂NO₃, molecular weight 316.18 g/mol. Soluble in DMSO and aqueous vehicles.
Mechanism of Action: The anti-Parkinsonian effect is thought to occur through reducing GABA release at the striatum-pallidus synapse, modulating the overactive indirect pathway in the basal ganglia. Research Applications: Parkinson's disease, drug addiction (morphine seeking/extinction), and substance use disorder models. Storage: Powder at -20°C (3 years), 4°C (2 years); in solvent at -80°C (6 months), -20°C (1 month). VU-0155041 is also known as VU0155041. It is a research compound used primarily for studying the role of mGluR4 in CNS disorders, particularly Parkinson's disease. Its potent and selective positive allosteric modulation of mGluR4 makes it a valuable tool for exploring new therapeutic strategies for Parkinson's disease and other disorders involving glutamatergic signaling. The compound is not approved for clinical use. |
| Molecular Formula |
C14H15CL2NO3
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|---|---|
| Molecular Weight |
316.178
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| Exact Mass |
315.043
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| Elemental Analysis |
C, 53.18; H, 4.78; Cl, 22.42; N, 4.43; O, 15.18
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| CAS # |
1093757-42-6
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| Related CAS # |
(1R,2S)-VU0155041; 1263273-14-8; VU0155041 sodium; 1259372-69-4
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| PubChem CID |
888023
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| Appearance |
Pale purple to purple solid powder
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| LogP |
4.472
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
20
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| Complexity |
367
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| Defined Atom Stereocenter Count |
2
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| SMILES |
ClC1=CC(NC([C@H]2[C@@H](C(O)=O)CCCC2)=O)=CC(Cl)=C1
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| InChi Key |
VSMUYYFJVFSVCA-NWDGAFQWSA-N
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| InChi Code |
InChI=1S/C14H15Cl2NO3/c15-8-5-9(16)7-10(6-8)17-13(18)11-3-1-2-4-12(11)14(19)20/h5-7,11-12H,1-4H2,(H,17,18)(H,19,20)/t11-,12+/m0/s1
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| Chemical Name |
(1R,2S)-2-[(3,5-dichlorophenyl)carbamoyl]cyclohexane-1-carboxylic acid
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| Synonyms |
VU0155041; VU-0155041; VU 0155041
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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: ~100 mg/mL (~316.3 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.91 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 (7.91 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1628 mL | 15.8138 mL | 31.6276 mL | |
| 5 mM | 0.6326 mL | 3.1628 mL | 6.3255 mL | |
| 10 mM | 0.3163 mL | 1.5814 mL | 3.1628 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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