Sphingosine kinase is a conserved lipid kinase that catalyzes formation sphingosine-1-phosphate, which is a key promotor in cancer. SKI-II is an oral active and synthetic inhibitor of sphingosine kinase (SK) activity, with IC50 values of 78 μM and 45 μM for SK1 and for SK2, respectively. SKI II causes an irreversible inhibition of SK1 by inducing its lysosomal and/or proteasomal degradation. SKI II (1.25 μM, 48 h) in combination with DDP has a clear synergistic effect in human gastric carcinoma SGC7901/DDP cell line[3]. Chronic SKI II (50.0 mg/kg, 3-weekly i.p. for 16 weeks) administration leads to permanent reduction of S1P concentrations in plasma in mice[4]. SKI II (50.0 mg/kg, IP; 100 mg/kg, PO) treatment reduces tumor growth in mice bearing solid tumor model[5].
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