Novel antagonist of the type 2 lysophosphatidic acid receptor (LPA), UCM-14216, ameliorates spinal cord injury in mice
| Autor: | 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, Rubén, López-Rodríguez, María L., Ortega-Gutiérrez, Silvia |
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| Rok vydání: | 2022 |
| Zdroj: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona |
| Popis: | Altres ajuts: this work has been supported by the Spanish Ministerio de Ciencia, Innovación y Universidades to R.L.-V., predoctoral FPU grants to N.K.-F., D.Z., and A.E.-P., and Juan de la Cierva postdoctoral fellowship to R.F.M. And R.L.-V. is the recipient of an ICREA Academia award. 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 (LPA) 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 LPA antagonists, among which compound 54 (UCM-14216) stands out as a potent and selective LPA receptor antagonist (E = 90%, IC = 1.9 μM, K = 1.3 nM; inactive at LPA receptors). This compound shows efficacy in an in vivo mouse model of SCI in an LPA-dependent manner, confirming the potential of LPA inhibition for providing a new alternative for treating SCI. |
| Databáze: | OpenAIRE |
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