W146 is a sphingosine-1-phosphate receptor 1 (S1P1) antagonist (Ki = 77 nM).1 It is selective for S1P1 over S1P2, S1P3, and S1P5 receptors (Kis = >10 µM for all). W146 prevents ligand-induced receptor internalization in CHO cells and inhibits the phosphorylation of ERK1 and Akt when used at a concentration of 10 µM. W146 (5 mg/kg) increases AMD3100-induced Kit+/Sca-1+/Lin− hematopoietic stem progenitor cell (KSL-HSPC) entrance into mouse blood circulation from the bone marrow when administered in combination with the chemokine (C-X-C motif) receptor 4 (CXCR4) antagonist and stem cell-mobilizer AMD3100.2 Intranasal or intradermal administration of W146 (10 µg) also disrupts the endothelial barrier and induces the infiltration of polymorphonuclear (PMN) neutrophils into the lungs and skin in an ovalbumin-induced mouse model of immune cell-mediated vascular injury.
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