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SKI II

SKU: orb1222379

Description

SKI-II is a selective non-lipid inhibitor of sphingosine kinase (IC50 = 0.5 μM). nhibits acute myelogenous leukemia cell growth in vitro and in vivo. SKI-II was more efficient than two known SphK1 inhibitors SK1-I and FTY720 in inhibiting AML cells. Meanwhile, it induced dramatic apoptosis in above AML cells, and the cytotoxicity by SKI-II was almost reversed by the general caspase inhibitor z-VAD-fmk. SKI-II treatment inhibited SphK1 activation, and concomitantly increased level of sphingosine-1-phosphate (S1P) precursor ceramide in AML cells.
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Images & Validation

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SKI II

Key Properties

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CAS Number312636-16-1
MW302.78
Purity>98% (HPLC)
FormulaC15H11ClN2OS
SMILESc1cc(ccc1c1csc(n1)Nc1ccc(cc1)O)Cl
TargetSphK1
SolubilityDMSO : ≥ 100 mg/mL; 330.27 mM

Bioactivity

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In Vivo
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. SKI II (50.0 mg/kg, IP; 100 mg/kg, PO) treatment reduces tumor growth in mice bearing solid tumor model. Animal model: 8 week-old female LDL-R-/-mice. Dosage: 50.0 mg/kg. Administration: IP injection daily, 3 days a week for 16 weeks. Result: A single administration of produced a significant reduction of plasma S1P with the maximum (~40%) observed 12 h after injection. At sacrifice (72 h after last injection) S1P levels were 266 ± 18 ng/mL and 328 ± 30 ng/mL in the SKI-II-treated and control groups, respectively. Animal model: BALB/c mouse solid tumor model that uses JC mammary adenocarcinoma cells. Dosage: 50.0 mg/kg. Administration: IP injection daily, 3 days a week for 16 weeks. Result: Had strong inhibition of tumor growth from the start of treatment of 65%, with no toxicity or weight loss. Animal model: BALB/c JC tumor model. Dosage: 100 mg/kg. Administration: PO every other day. Result: Caused significant antitumor activity in well-established tumors as early as day 5, with maximal response seen at the end of the study. Showed 79% inhibition of tumor growth from the start of treatment.
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In Vitro
SKI II inhibits cell proliferation by suppressing the Wnt/β-catenin signaling pathway. SKI II promotes the degradation of β-catenin by enhancing Wnt5A. SKI II (1.25 μM, 48 h) in combination with DDP has a clear synergistic effect in human gastric carcinoma SGC7901/DDP cell line. Cell Cytotoxicity Assay Cell line: The human gastric carcinoma SGC7901/DDP cell line. Concentration: 0 μM, 1.25 μM (combined with DDP). Incubation time: 48 hours. Result: SKI II in combination with DDP had a greater effect on the SGC-7901/DDP cells compared with DDP or SKI II alone.
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Storage & Handling

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StorageStorage temperature: -20°C. Stability: ≥ 2 years
Expiration Date12 months from date of receipt.
DisclaimerFor research use only

Alternative Names

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SKI-II | SKI II. Sphingosine kinase inhibitor II

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Quick Database Links

Gene Symbol
SphK1

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SKI II (orb1222379)

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