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ID: ALA1138961

Journal: Bioorg Med Chem Lett

Title: Highly selective and potent agonists of sphingosine-1-phosphate 1 (S1P1) receptor.

Authors: Vachal P, Toth LM, Hale JJ, Yan L, Mills SG, Chrebet GL, Koehane CA, Hajdu R, Milligan JA, Rosenbach MJ, Mandala S.

Abstract: Novel series of sphingosine-1-phosphate (S1P) receptor agonists were developed through a systematic SAR aimed to achieve high selectivity for a single member of the S1P family of receptors, S1P1. The optimized structure represents a highly S1P1-selective and efficacious agonist: S1P1/S1P2, S1P1/S1P3, S1P1/S1P4>10,000-fold, S1P1/S1P5>600-fold, while EC50 (S1P1) <0.2 nM. In vivo experiments are consistent with S1P1 receptor agonism alone being sufficient for achieving desired lymphocyte-lowering effect.

CiteXplore: 16682185

DOI: 10.1016/j.bmcl.2006.04.064