| Literature DB >> 17114004 |
Shifeng Pan1, Yuan Mi, Charles Pally, Christian Beerli, Alice Chen, Danilo Guerini, Klaus Hinterding, Barbara Nuesslein-Hildesheim, Tove Tuntland, Sophie Lefebvre, Yi Liu, Wenqi Gao, Alan Chu, Volker Brinkmann, Christian Bruns, Markus Streiff, Catherine Cannet, Nigel Cooke, Nathanael Gray.
Abstract
FTY720 is an immunomodulator with demonstrated efficacy in a phase II trial of relapsing multiple sclerosis. FTY720-phosphate, the active metabolite generated upon phosphorylation in vivo, acts as a potent agonist on four of the five known sphingosine-1-phosphate (S1P(1)) receptors. AUY954, an aminocarboxylate analog of FTY720, is a low nanomolar, monoselective agonist of the S1P(1) receptor. Due to its selectivity and pharmacokinetic profile, AUY954 is an excellent pharmacological probe of S1P(1)-dependent phenomena. Oral administration of AUY954 induces a profound and reversible reduction of circulating lymphocytes and, in combination with RAD001 (Certican/Everolimus, an mTOR inhibitor), is capable of prolonging the survival of cardiac allografts in a stringent rat transplantation model. This demonstrates that a selective agonist of the S1P(1) receptor is sufficient to achieve efficacy in an animal model of transplantation.Entities:
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Year: 2006 PMID： 17114004 DOI： 10.1016/j.chembiol.2006.09.017
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521