IC50: 2 μM (GST-hSK), 6 μM (hPI3k) and 80 μM (ERK2)

SKI V (75 mg/kg; i.p.; days 1, 5, 9, 15) significantly lowers tumor growth (>50% decreased at day 18) than control animals. Animal Model: 6-8 weeks old BALB/c female mice with JC mammary adenocarcinoma cells Dosage: 75 mg/kg Administration: IP; days 1, 5, 9, 15 Result: Tumor growth was significantly lower (>50% decreased at day 18) than tumor growth in control animals.

SKI V has weak activity toward ERK2 ( IC 50 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. SKI V has IC 50 s 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. Cell Proliferation Assay Cell Line: T24 tumor cells Concentration: 10 μM Incubation Time: For 24 hours Result: Inhibited cancer cell proliferation. Apoptosis Analysis Cell Line: T24 tumor cells Concentration: 10 μM Incubation Time: For 24 hours Result: Induced apoptosis. Western Blot Analysis Cell Line: JC cells Concentration: 0.2, 1, 5 μM Incubation Time: Pretreated for 1 hour Result: Decreased phospho-Akt and phospho-MEK levels.

SKI V 是一种非竞争性的，有效的非脂质鞘氨醇激酶 (SPHK; SK) 抑制剂，对 GST-hSK 的 IC50 为 2 μM。 SKI V 有效抑制 PI3K，对 hPI3k 的 IC50 为 6 μM。SKI V 减少有丝分裂的第二信使鞘氨醇-1-磷酸 (S1P) 的形成。SKI V 诱导细胞凋亡 (apoptosis) 并具有抗肿瘤活性。