VU0155041

VU0155041
Identifiers
	IUPAC name (1R,2S)-2-[(3,5-dichlorophenyl)carbamoyl]cyclohexane-1-carboxylic acid;
CAS Number	1263273-14-8;
PubChem CID	888023;
IUPHAR/BPS	3323;
ChemSpider	776108;
ChEMBL	ChEMBL578988;
Chemical and physical data
Formula	C14H15Cl2NO3
Molar mass	316.18 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1CC[C@H]([C@H](C1)C(=O)NC2=CC(=CC(=C2)Cl)Cl)C(=O)O;
	InChI 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; Key:VSMUYYFJVFSVCA-NWDGAFQWSA-N;

VU0155041 is an experimental drug that is a positive allosteric modulator for the glutamate receptor mGluR4. In animal studies it has anti-Parkinsonian action, reduces neuropathic pain such as allodynia, and counteracts the effects of opioid addiction.^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]

References

^ Niswender CM, Johnson KA, Weaver CD, Jones CK, Xiang Z, Luo Q, et al. (November 2008). "Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4". Molecular Pharmacology. 74 (5): 1345–1358. doi:10.1124/mol.108.049551. PMC 2574552. PMID 18664603.
^ Williams R, Johnson KA, Gentry PR, Niswender CM, Weaver CD, Conn PJ, et al. (September 2009). "Synthesis and SAR of a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor 4 (mGluR4)". Bioorganic & Medicinal Chemistry Letters. 19 (17): 4967–4970. doi:10.1016/j.bmcl.2009.07.072. PMC 2752865. PMID 19640716.
^ Wang H, Jiang W, Yang R, Li Y (March 2011). "Spinal metabotropic glutamate receptor 4 is involved in neuropathic pain". NeuroReport. 22 (5): 244–248. doi:10.1097/WNR.0b013e3283453843. PMID 21358553.
^ Betts MJ, O'Neill MJ, Duty S (August 2012). "Allosteric modulation of the group III mGlu4 receptor provides functional neuroprotection in the 6-hydroxydopamine rat model of Parkinson's disease". British Journal of Pharmacology. 166 (8): 2317–2330. doi:10.1111/j.1476-5381.2012.01943.x. PMC 3448896. PMID 22404342.
^ Becker JA, Clesse D, Spiegelhalter C, Schwab Y, Le Merrer J, Kieffer BL (August 2014). "Autistic-like syndrome in mu opioid receptor null mice is relieved by facilitated mGluR4 activity". Neuropsychopharmacology. 39 (9): 2049–2060. doi:10.1038/npp.2014.59. PMC 4104328. PMID 24619243.
^ Ebrahimi Z, Kahvandi N, Komaki A, Karimi SA, Naderishahab M, Sarihi A (March 2021). "The role of mGlu4 receptors within the nucleus accumbens in acquisition and expression of morphine-induced conditioned place preference in male rats". BMC Neuroscience. 22 (1): 17. doi:10.1186/s12868-021-00627-2. PMC 7981834. PMID 33743609.
^ Becker JA, Pellissier LP, Corde Y, Laboute T, Léauté A, Gandía J, et al. (June 2021). "Facilitating mGluR4 activity reverses the long-term deleterious consequences of chronic morphine exposure in male mice". Neuropsychopharmacology. 46 (7): 1373–1385. doi:10.1038/s41386-020-00927-x. PMC 8136479. PMID 33349673.
^ Ebrahimi Z, Kahvandi N, Shahriari E, Komaki A, Karimi SA, Naderishahab M, et al. (June 2023). "VU0155041, a positive allosteric modulator of mGluR4, in the nucleus accumbens facilitates extinction and inhibits the reinstatement of morphine-induced conditioned place preference in male rats". Brain Research Bulletin. 197: 57–64. doi:10.1016/j.brainresbull.2023.03.012. PMID 36997034.
^ Xu YL, Xia YT, Zhang MM, Li YJ, Tao XX, Li K, et al. (June 2025). "Red nucleus mGluR4 and mGluR8 inhibit nociception and the development of neuropathic pain by restraining the expressions of TNF-α and IL-1β". Neuropharmacology. 271: 110387. doi:10.1016/j.neuropharm.2025.110387. PMID 40010564.

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[1] Niswender CM, Johnson KA, Weaver CD, Jones CK, Xiang Z, Luo Q, et al. (November 2008). "Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4". Molecular Pharmacology. 74 (5): 1345–1358. doi:10.1124/mol.108.049551. PMC 2574552. PMID 18664603.

[2] Williams R, Johnson KA, Gentry PR, Niswender CM, Weaver CD, Conn PJ, et al. (September 2009). "Synthesis and SAR of a novel positive allosteric modulator (PAM) of the metabotropic glutamate receptor 4 (mGluR4)". Bioorganic & Medicinal Chemistry Letters. 19 (17): 4967–4970. doi:10.1016/j.bmcl.2009.07.072. PMC 2752865. PMID 19640716.

[3] Wang H, Jiang W, Yang R, Li Y (March 2011). "Spinal metabotropic glutamate receptor 4 is involved in neuropathic pain". NeuroReport. 22 (5): 244–248. doi:10.1097/WNR.0b013e3283453843. PMID 21358553.

[4] Betts MJ, O'Neill MJ, Duty S (August 2012). "Allosteric modulation of the group III mGlu4 receptor provides functional neuroprotection in the 6-hydroxydopamine rat model of Parkinson's disease". British Journal of Pharmacology. 166 (8): 2317–2330. doi:10.1111/j.1476-5381.2012.01943.x. PMC 3448896. PMID 22404342.

[5] Becker JA, Clesse D, Spiegelhalter C, Schwab Y, Le Merrer J, Kieffer BL (August 2014). "Autistic-like syndrome in mu opioid receptor null mice is relieved by facilitated mGluR4 activity". Neuropsychopharmacology. 39 (9): 2049–2060. doi:10.1038/npp.2014.59. PMC 4104328. PMID 24619243.

[6] Ebrahimi Z, Kahvandi N, Komaki A, Karimi SA, Naderishahab M, Sarihi A (March 2021). "The role of mGlu4 receptors within the nucleus accumbens in acquisition and expression of morphine-induced conditioned place preference in male rats". BMC Neuroscience. 22 (1): 17. doi:10.1186/s12868-021-00627-2. PMC 7981834. PMID 33743609.

[7] Becker JA, Pellissier LP, Corde Y, Laboute T, Léauté A, Gandía J, et al. (June 2021). "Facilitating mGluR4 activity reverses the long-term deleterious consequences of chronic morphine exposure in male mice". Neuropsychopharmacology. 46 (7): 1373–1385. doi:10.1038/s41386-020-00927-x. PMC 8136479. PMID 33349673.

[8] Ebrahimi Z, Kahvandi N, Shahriari E, Komaki A, Karimi SA, Naderishahab M, et al. (June 2023). "VU0155041, a positive allosteric modulator of mGluR4, in the nucleus accumbens facilitates extinction and inhibits the reinstatement of morphine-induced conditioned place preference in male rats". Brain Research Bulletin. 197: 57–64. doi:10.1016/j.brainresbull.2023.03.012. PMID 36997034.

[9] Xu YL, Xia YT, Zhang MM, Li YJ, Tao XX, Li K, et al. (June 2025). "Red nucleus mGluR4 and mGluR8 inhibit nociception and the development of neuropathic pain by restraining the expressions of TNF-α and IL-1β". Neuropharmacology. 271: 110387. doi:10.1016/j.neuropharm.2025.110387. PMID 40010564.

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