Gonzalez-Gil, InesZian, DeboraVazquez-Villa, HenarHernandez-Torres, GloriaMartinez, R FernandoKhiar-Fernandez, NoraRivera, RichardKihara, YasuyukiDevesa, IsabelMathivanan, SakthikumarDel Valle, Cristina RosellZambrana-Infantes, EmmaPuigdomenech, MariaCincilla, GiovanniSanchez-Martinez, MelchorRodriguez de Fonseca, FernandoFerrer-Montiel, Antonio VChun, JeroldLopez-Vales, RubenLopez-Rodriguez, Maria LOrtega-Gutierrez, Silvia2023-02-082023-02-082019-12-16González-Gil I, Zian D, Vázquez-Villa H, Hernández-Torres G, Martínez RF, Khiar-Fernández N, et al. A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA1), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration. J Med Chem. 2020 Mar 12;63(5):2372-2390http://hdl.handle.net/10668/14777Neuropathic pain (NP) is a complex chronic pain state with a prevalence of almost 10% in the general population. Pharmacological options for NP are limited and weakly effective, so there is a need to develop more efficacious NP attenuating drugs. Activation of the type 1 lysophosphatidic acid (LPA1) receptor is a crucial factor in the initiation of NP. Hence, it is conceivable that a functional antagonism strategy could lead to NP mitigation. Here we describe a new series of LPA1 agonists among which derivative (S)-17 (UCM-05194) stands out as the most potent and selective LPA1 receptor agonist described so far (Emax = 118%, EC50 = 0.24 μM, KD = 19.6 nM; inactive at autotaxin and LPA2-6 receptors). This compound induces characteristic LPA1-mediated cellular effects and prompts the internalization of the receptor leading to its functional inactivation in primary sensory neurons and to an efficacious attenuation of the pain perception in an in vivo model of NP.enAnalgesicsAnimalsCell lineCell movementCells, culturedAnalgesicsAnimalsCell LineCell movementCells, culturedDrug discoveryFemaleHumansHydrocarbons, aromaticMice, inbred C57BLModels, molecularNeuralgiaPain perceptionRats, wistarReceptors, lysophosphatidic acidSensory receptor cellsresearch article31790581open accessAnalgésicosCélulas cultivadasCélulas receptoras sensorialesDescubrimiento de drogasHidrocarburos aromáticosLínea celularModelos molecularesMovimiento celularNeuralgiaPercepción del dolorRatas wistarRatones Endogámicos C57BLReceptores del acido lisofosfatídico10.1021/acs.jmedchem.9b012871520-4804PMC7344333https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344333https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344333/pdf