Título : A novel agonist of the type 1 lysophosphatidic acid receptor
(LPA1), UCM-05194, shows efficacy in neuropathic pain
amelioration |
Autor : González-Gil, Inés Zian, Debora  Vázquez-Villa, Henar  Hernández-Torres, Gloria Martínez, Fernando KHIAR FERNÁNDEZ, NORA  Rivera, Richard  Kihara, Yasuyuki  Devesa Giner, Isabel  |
Editor : American Chemical Society |
Departamento: Departamentos de la UMH::Bioquímica y Biología Molecular |
Fecha de publicación: 2019-12 |
URI : https://hdl.handle.net/11000/35284 |
Resumen :
Neuropathic 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 slightly effective, so there is a
need of developing 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
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Área de conocimiento : CDU: Ciencias puras y naturales: Biología: Bioquímica. Biología molecular. Biofísica |
Tipo de documento : info:eu-repo/semantics/article |
Derechos de acceso: info:eu-repo/semantics/closedAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional |
DOI : https://doi.org/10.1021/acs.jmedchem.9b01287 |
Publicado en: J Med Chem. 2020 March 12; 63(5): 2372–2390 |
Aparece en las colecciones: Artículos Bioquímica y Biología Molecular
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