SKI II

SKI-II is a synthetic inhibitor of sphingosine kinase (SK) activity with IC50 of 78 M for SK1 and 45 M for SK2.

SKI II inhibits cell proliferation by suppressing the Wnt/-catenin signaling pathway. SKI II also reduces the expression of c-Myc and cyclin D1, the downstream target genes of the Wnt signaling pathway. SKI II inhibits cell proliferation by suppressing the Wnt/-catenin signaling pathway. SKI II promotes the degradation of -catenin by enhancing Wnt5A. SKI II inhibits the proliferation of HepG2 cells by blocking the Wnt/-catenin signaling pathway.

SKI-II causes an irreversible inhibition of SK1 by inducing its lysosomal and/or proteasomal degradation. In the present study, SKI-II was administered 3-weekly i.p. to LDL-R-/- mice for 16 weeks at a dose previously demonstrated to reduce tumor growth in mice. Preliminary experiments revealed that a single administration of SKI-II produces a significant reduction of plasma S1P with the maximum (40%) observed 12 h after injection.