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Selectivity and specificity of sphingosine 1-phosphate receptor ligands : "off-targets" or complex pharmacology?

Pyne, Nigel J and Pyne, Susan (2011) Selectivity and specificity of sphingosine 1-phosphate receptor ligands : "off-targets" or complex pharmacology? Frontiers in Pharmacology, 2.

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Abstract

A recent perspective published in Frontiers of Pharmacology by Salomone and Waeber (2011) discussed the selectivity and specificity of sphingosine 1-phosphate (S1P) receptor ligands. This perspective surveyed the use of various S1P receptor ligands and attempted to reconcile a number of inconsistencies in the predicted biological outcomes: these were interpreted as "off-target" effects. Therefore the perspective cautioned against the use of these S1P receptor ligands. Here we highlight the complex pharmacology of S1P receptors, which along with "inside-out" signaling might provide an alternative explanation for "off-target" effects.