SKI II

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

SKI II 是一种高选择性、非 ATP 竞争性 S1P 受体抑制剂 (IC50: 0.5 μM)，同时对其他激酶（包括 PKCα、PI3K 和 ERK2）没有抑制作用。

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.

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.

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.

SKI-II | SKI II. Sphingosine kinase inhibitor II

Others

Other Targets

SphK1

Cancer

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312636-16-1

302.78

C15H11ClN2OS

>98% (HPLC)

DMSO : ≥ 100 mg/mL; 330.27 mM

c1cc(ccc1c1csc(n1)Nc1ccc(cc1)O)Cl

4-[[4-(4-Chlorophenyl)-2-thiazolyl]amino]phenol

(-20℃)

With Ice Pack

≥ 2 years