Document Report Card

ID: ALA5120964

Journal: J Med Chem

Title: Novel Antagonist of the Type 2 Lysophosphatidic Acid Receptor (LPA₂), UCM-14216, Ameliorates Spinal Cord Injury in Mice.

Authors: Khiar-Fernández N, Zian D, Vázquez-Villa H, Martínez RF, Escobar-Peña A, Foronda-Sainz R, Ray M, Puigdomenech-Poch M, Cincilla G, Sánchez-Martínez M, Kihara Y, Chun J, López-Vales R, López-Rodríguez ML, Ortega-Gutiérrez S.

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 (E_max = 90%, IC₅₀ = 1.9 μM, K_D = 1.3 nM; inactive at LPA_1,3-6 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.

CiteXplore: 35948083

DOI: 10.1021/acs.jmedchem.2c00046