Details

Autor(en) / Beteiligte

• Khiar-Fernández, Nora
• Zian, Debora
• Vázquez-Villa, Henar
• Martínez, R. 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

Titel

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

Ist Teil von

• Journal of medicinal chemistry, 2022-08, Vol.65 (16), p.10956-10974

Ort / Verlag

American Chemical Society

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 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.