| Literature DB >> 22999882 |
Jean Quancard1, Birgit Bollbuck, Philipp Janser, Daniela Angst, Frédéric Berst, Peter Buehlmayer, Markus Streiff, Christian Beerli, Volker Brinkmann, Danilo Guerini, Paul A Smith, Timothy J Seabrook, Martin Traebert, Klaus Seuwen, René Hersperger, Christian Bruns, Frédéric Bassilana, Marc Bigaud.
Abstract
Lymphocyte trafficking is critically regulated by the Sphingosine 1-phosphate receptor-1 (S1P(1)), a G protein-coupled receptor that has been highlighted as a promising therapeutic target in autoimmunity. Fingolimod (FTY720, Gilenya) is a S1P(1) receptor agonist that has recently been approved for the treatment of multiple sclerosis (MS). Here, we report the discovery of NIBR-0213, a potent and selective S1P(1) antagonist that induces long-lasting reduction of peripheral blood lymphocyte counts after oral dosing. NIBR-0213 showed comparable therapeutic efficacy to fingolimod in experimental autoimmune encephalomyelitis (EAE), a model of human MS. These data provide convincing evidence that S1P(1) antagonists are effective in EAE. In addition, the profile of NIBR-0213 makes it an attractive candidate to further study the consequences of S1P(1) receptor antagonism and to differentiate the effects from those of S1P(1) agonists.Entities:
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Year: 2012 PMID： 22999882 DOI： 10.1016/j.chembiol.2012.07.016
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521