2026-06-05T18:42:42Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/719032024-10-03T15:58:32Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Khiar Fernández, Nora author Zian, Debora author Vázquez Villa, María Del Henar author Martínez, R. Fernando author Escobar Peña, Ana Andrea author Foronda Sainz, Román author Ray, Manisha author Puigdomenech Poch, Maria author Cincilla, Giovanni author Sánchez Martínez, Melchor author Kihara, Yasuyuki author Chun, Jerold author López Vales, Rubèn author López Rodríguez, María Luz author Ortega Gutiérrez, Silvia author 2022-08-10 Spinal cord injuries (SCIs) irreversibly disrupt spinal connectivity, leading to permanent neurological disabilities. Current medical treatments for reducing the secondary damage that follows the initial injury are limited to surgical decompression and anti-inflammatory drugs, so there is a pressing need for new therapeutic strategies. Inhibition of the type 2 lysophosphatidic acid receptor (LPA2) has recently emerged as a new potential pharmacological approach to decrease SCIassociated damage. Toward validating this receptor as a target in SCI, we have developed a new series of LPA2 antagonists, among which compound 54 (UCM14216) stands out as a potent and selective LPA2 receptor antagonist (Emax = 90%, IC50 = 1.9 μM, KD = 1.3 nM; inactive at LPA1,3−6 receptors). This compound shows efficacy in an in vivo mouse model of SCI in an LPA2-dependent manner, confirming the potential of LPA2 inhibition for providing a new alternative for treating SCI. 0022-2623 10.1021/acs.jmedchem.2c00046 https://hdl.handle.net/20.500.14352/71903 https://doi.org/10.1021/acs.jmedchem.2c00046 Novel Antagonist of the Type 2 Lysophosphatidic Acid Receptor (LPA2), UCM-14216, Ameliorates Spinal Cord Injury in Mice