Author/Authors :
Jean Quancard، نويسنده , , Birgit Bollbuck، نويسنده , , Philipp Janser، نويسنده , , Daniela Angst، نويسنده , , Frédéric Berst، نويسنده , , Peter Buehlmayer، نويسنده , , Markus Streiff، نويسنده , , Christian Beerli، نويسنده , , Volker Brinkmann، نويسنده , , Danilo Guerini، نويسنده , , Paul A. Smith، نويسنده , , Timothy J. Seabrook، نويسنده , , Martin Traebert، نويسنده , , Klaus Seuwen، نويسنده , , Rene Hersperger، نويسنده , , Christ، نويسنده ,
Abstract :
Lymphocyte trafficking is critically regulated by the Sphingosine 1-phosphate receptor-1 (S1P1), a G protein-coupled receptor that has been highlighted as a promising therapeutic target in autoimmunity. Fingolimod (FTY720, Gilenya) is a S1P1 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 S1P1 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 S1P1 antagonists are effective in EAE. In addition, the profile of NIBR-0213 makes it an attractive candidate to further study the consequences of S1P1 receptor antagonism and to differentiate the effects from those of S1P1 agonists.
