SKI-II

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.

Product information

CAS Number: 312636-16-1

Molecular Weight: 302.78

Formula: C15H11ClN2OS

Chemical Name: 4-[[4-(4-Chlorophenyl)-2-thiazolyl]amino]phenol

Smiles: OC1C=CC(=CC=1)NC1=NC(=CS1)C1C=CC(Cl)=CC=1

InChiKey: ZFGXZJKLOFCECI-UHFFFAOYSA-N

InChi: InChI=1S/C15H11ClN2OS/c16-11-3-1-10(2-4-11)14-9-20-15(18-14)17-12-5-7-13(19)8-6-12/h1-9,19H,(H,17,18)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

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.

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.

References:

1. Yang L, Weng W, Sun ZX, Fu XJ, Ma J, Zhuang WF. SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo. Biochem Biophys Res Commun. 2015 May 15;460(4):903-8. doi: 10.1016/j.bbrc.2015.03.114. Epub 2015 Mar 28. PubMed PMID: 25824043.
2. Li PH, Wu JX, Zheng JN, Pei DS. A sphingosine kinase-1 inhibitor, SKI-II, induces growth inhibition and apoptosis in human gastric cancer cells. Asian Pac J Cancer Prev. 2014;15(23):10381-5. PubMed PMID: 25556479.
3. Liu Y, Zhu Z, Cai H, Liu Q, Zhou H, Zhu Z. SKI-II reverses the chemoresistance of SGC7901/DDP gastric cancer cells. Oncol Lett. 2014 Jul;8(1):367-373. Epub 2014 Apr 25. PubMed PMID: 24959278; PubMed Central PMCID: PMC4063656.

Products are for research use only. Not for human use.