Fiche publication
Date publication
juin 2019
Journal
The Journal of pharmacology and experimental therapeutics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr PEYRIN-BIROULET Laurent
Tous les auteurs :
Al-Shamma H, Lehmann-Bruinsma K, Carroll C, Solomon M, Komori HK, Peyrin-Biroulet L, Adams J
Lien Pubmed
Résumé
Lymphocyte trafficking out of secondary lymphoid organs is regulated by concentration gradient-dependent interactions between the membrane-derived lysophospholipid signaling molecule sphingosine 1-phosphate (S1P) and the G-protein-coupled receptor, S1P Etrasimod is a novel, next-generation, small-molecule, oral S1P receptor modulator in clinical development for the treatment of immune-mediated inflammatory disorders, including ulcerative colitis. In preclinical pharmacology studies, etrasimod was a full agonist of recombinant human (6.1 nM EC), mouse (3.65 nM EC), dog (4.19 nM EC), and monkey (8.7 nM EC) S1P receptors, and a partial agonist of human S1P (147 nM EC) and S1P (24.4 nM EC), with relative efficacies of 63% and 73% of S1P response, respectively; whereas neither agonist nor antagonist activity was observed for human S1P or S1P A dose-dependent relationship was observed for etrasimod plasma concentration and lymphocyte count in mice, and chronic treatment with etrasimod resulted in attenuation of inflammation in a CD4CD45RB T-cell transfer mouse model of colitis.
Référence
J. Pharmacol. Exp. Ther.. 2019 Jun;369(3):311-317
