SKI V is a noncompetitive and potent non-lipid sphingosine kinase (SPHK; SK) inhibitor with an IC50 of 2 μM for GST-hSK. SKI V potently inhibits PI3K with an IC50 of 6 μM for hPI3k. SKI V decreases formation of the mitogenic second messenger sphingosine-1-phosphate (S1P). SKI V induces apoptosis and has antitumor activity[2].IC50 & Target: IC50: 2 μM (GST-hSK), 6 μM (hPI3k) and 80 μM (ERK2)In Vitro: SKI V has weak activity toward ERK2 (IC50 of 80 μM for hERK2) and does not inhibit PKC-α.
SKI V (10 μM; for 24 hours) inhibits cancer cell proliferation and induces apoptosis.
SKI V (0.2, 1, 5 μM; pretreated for 1 hour) decreases phospho-Akt and phospho-MEK levels. Near-confluent cultures of JC cells are serum-starved for 16 hours, followed by pretreatment SKI V for 1 hour[2].
SKI V has IC50s for inhibition of sphingosine kinase (SK) and tumor cell proliferation of ～2 μM.
SKI V (20 μg/ml) inhibits not only purified but endogenous SK in in MDA-MB-231 cells.
SKI V (0.2, 1, 5 μM) inhibits intracellular S1P formation in JC cells in a dose-dependent fashion[2].
In Vivo: SKI V (75 mg/kg; i.p.; days 1, 5, 9, 15) significantly lowers tumor growth (>50% decreased at day 18) than control animals.