%0 Journal Article %A Hussien Al-Shamma %A Karin Lehmann-Bruinsma %A Chris Carroll %A Michelle Solomon %A H. Kiyomi Komori %A Laurent Peyrin-Biroulet %A John Adams %T The Selective Sphingosine 1-phosphate Receptor Modulator Etrasimod Regulates Lymphocyte Trafficking and Alleviates Experimental Colitis %D 2019 %R 10.1124/jpet.118.254268 %J Journal of Pharmacology and Experimental Therapeutics %P jpet.118.254268 %X 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, S1P1. 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 EC50), mouse (3.65 nM EC50), dog (4.19 nM EC50) and monkey (8.7 nM EC50) S1P1 receptors, and a partial agonist of human S1P4 (147 nM EC50 ) and S1P5 (24.4 nM EC50), with relative efficacies of 63% and 73% of S1P response respectively, whereas neither agonist nor antagonist activity was observed for human S1P2 or S1P3. 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 CD4+CD45RBhigh T cell transfer mouse model of colitis. %U https://jpet.aspetjournals.org/content/jpet/early/2019/03/14/jpet.118.254268.full.pdf