RT Journal Article
T1 A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA1), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration
A1 González Gil, Inés
A1 Zian, Debora
A1 Vázquez Villa, María Del Henar
A1 Hernández Torres, Gloria
A1 Martínez, R. Fernando
A1 Khiar Fernández, Nora
A1 Rivera, Richard
A1 Kihara, Yasuyuki
A1 Devesa, Isabel
A1 Mathivanan, Sakthikumar
A1 Rosell del Valle, Cristina
A1 Zambrana Infantes, Emma
A1 Puigdomenech, María
A1 Cincilla, Giovanni
A1 Sánchez Martínez, Melchor
A1 Rodríguez De Fonseca, Fernando Antonio
A1 Ferrer Montiel, Antonio V.
A1 Chun, Jerold
A1 López Vales, Ruben
A1 López Rodríguez, María Luz
A1 Ortega Gutiérrez, Silvia
AB ABSTRACT: Neuropathic pain (NP) is a complex chronicpain state with a prevalence of almost 10% in the generalpopulation. Pharmacological options for NP are limited andweakly effective, so there is a need to develop more efficaciousNP attenuating drugs. Activation of the type 1 lysophosphatidic acid (LPA1) receptor is a crucial factor in the initiation ofNP. Hence, it is conceivable that a functional antagonismstrategy could lead to NP mitigation. Here we describe a newseries of LPA1 agonists among which derivative (S)-17(UCM-05194) stands out as the most potent and selectiveLPA1 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-mediatedcellular effects and prompts the internalization of the receptor leading to its functional inactivation in primary sensory neuronsand to an efficacious attenuation of the pain perception in an in vivo model of NP.
PB American Chemical Society
YR 2019
FD 2019-12-02
LK https://hdl.handle.net/20.500.14352/103163
UL https://hdl.handle.net/20.500.14352/103163
LA eng
NO A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA1), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration Inés González-Gil, Debora Zian, Henar Vázquez-Villa, Gloria Hernández-Torres, R. Fernando Martínez, Nora Khiar-Fernández, Richard Rivera, Yasuyuki Kihara, Isabel Devesa, Sakthikumar Mathivanan, Cristina Rosell del Valle, Emma Zambrana-Infantes, María Puigdomenech, Giovanni Cincilla, Melchor Sanchez-Martinez, Fernando Rodríguez de Fonseca, Antonio V. Ferrer-Montiel, Jerold Chun, Rubén López-Vales, María L. López-Rodríguez, and Silvia Ortega-Gutiérrez Journal of Medicinal Chemistry 2020 63 (5), 2372-2390 DOI: 10.1021/acs.jmedchem.9b01287
DS Docta Complutense
RD 4 abr 2025