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http://hdl.handle.net/10662/21482
Title: | Novel Antagonist of the Type 2 Lysophosphatidic Acid Receptor (LPA2), UCM-14216, Ameliorates Spinal Cord Injury in Mice |
Authors: | Khiar Fernández, Nora Zian, Debora Vázquez Villa, Henar Martínez Vázquez, Rafael Fernando Escobar Peña, Andrea Foronda Sainz, Román Ray, Manisha Puigdomenech Poch, Maria Cincilla, Giovanni Sánchez Martínez, Melchor Kihara, Yasuyuki Chun, Jerold López Vales, Rubèn López Rodríguez, María L. Ortega Gutiérrez, Silvia |
Keywords: | Antagonists;Lipids;Receptors;Antagonistas;Lípidos;Receptores |
Issue Date: | 2022 |
Abstract: | 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 SCI-associated damage. Toward validating this receptor as a target in SCI, we have developed a new series of LPA2 antagonists, among which compound 54 (UCM-14216) 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. |
URI: | http://hdl.handle.net/10662/21482 |
DOI: | 10.1021/acs.jmedchem.2c00046 |
Appears in Collections: | DQOIN - Artículos |
Files in This Item:
File | Description | Size | Format | |
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LPA2-antagonists.pdf | Manuscript | 6,94 MB | Adobe PDF | View/Open |
acs_jmedchem_2c00046.pdf | 6,94 MB | Adobe PDF | View/Open |
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