SKI V is a highly potent noncompetitive inhibitor of non-lipid sphingosine kinase (SPHK; SK), with an IC50 of 2 μM for GST-hSK. Additionally, SKI V exhibits potent inhibition of PI3K, with an IC50 of 6 μM for hPI3K. It effectively reduces the formation of the mitogenic second messenger sphingosine-1-phosphate (S1P). SKI V demonstrates apoptotic induction and displays significant antitumor activity[1][2].
体内研究
SKI V (75 mg/kg; i.p.; days 1, 5, 9, 15) significantly reduces tumor growth (>50% decreased at day 18) compared to control animals[1].
体外研究
SKI V exhibits low activity against ERK2 (IC50 of 80 μM for hERK2) and it does not inhibit PKC-α[1].
SKI V (10 μM; 24-hour treatment) suppresses cancer cell proliferation and triggers apoptosis[1].
SKI V (0.2, 1, 5 μM; pretreated for 1 hour) reduces levels of phosphorylated Akt and phosphorylated MEK. Near-confluent JC cell cultures are serum-starved for 16 hours, then subjected to SKI V pretreatment for 1 hour[2].
SKI V exhibits IC50 values of approximately 2 μM for inhibiting sphingosine kinase (SK) and tumor cell proliferation[1].
SKI V (20 μg/ml) inhibits both purified and endogenous sphingosine kinase (SK) in MDA-MB-231 cells[1].
SKI V (0.2, 1, 5 μM) inhibits the formation of intracellular sphingosine-1-phosphate (S1P) in JC cells in a dose-dependent manner[2].
SKI V 细胞实验
Cell Line
Concentration
Treated Time
Description
References
PCCa-1 cells
1-30 µM
48-96 hours
SKI-V inhibited pCCa-1 cell viability in a concentration- and time-dependent manner.
Int J Biol Sci. 2022 Apr 18;18(7):2994-3005
C1 primary osteosarcoma cells
1-50 µM
48-96 hours
SKI-V significantly inhibited survival, growth, proliferation, and migration of C1 primary osteosarcoma cells, and induced cell death and apoptosis
Cell Death Discov. 2022 Feb 3;8(1):48
SKI V 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Nude mice
Subcutaneous cervical cancer xenograft model
Intraperitoneal injection
25 mg/kg
Daily for 15 days
SKI-V significantly inhibited the growth of subcutaneous pCCa-1 xenograft tumors.
Int J Biol Sci. 2022 Apr 18;18(7):2994-3005
Nude mice
Osteosarcoma xenograft model
Intraperitoneal injection
30 mg/kg
Once daily for 18 days
SKI-V significantly suppressed the growth of osteosarcoma xenograft tumors, with SphK1 inhibition, ceramide increase, and Akt-mTOR inhibition detected in tumor tissues
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