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UV0155041 is a potent, positive allosteric modulator/allosteric agonist at mGlu4 receptors (EC50 = 798 and 693 nM at human and rat mGlu4 receptors respectively).
VU0155041 (CAS: 1093757-42-6) is a synthetic small molecule characterized as a potent and selective positive allosteric modulator (PAM) of the metabotropic glutamate receptor subtype 4 (mGluR4). It is a cis-regioisomer based on a cyclohexylamide skeleton, discovered through high-throughput screening as a chemical tool to investigate the therapeutic potential of mGluR4 activation. Unlike some earlier mGluR4 modulators, VU0155041 exhibits improved aqueous solubility and selectivity, making it a valuable research compound for studying neurological disorders such as Parkinson's disease and substance use disorders.| 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. |
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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.
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| 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. |
| 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.
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| 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.
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| 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. |
| 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.
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| 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.
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| 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). |
| 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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