For research use only. Not for therapeutic Use.
<p style=/line-height:25px/>SKI-II is a synthetic inhibitor of sphingosine kinase (SK) activity with IC50 of 78 μM for SK1 and 45 μM for SK2.<br>IC50 value: 78/45 μM (SK1/2) [2]<br>Target: SK<br>in vitro: SKI II inhibits cell proliferation by suppressing the Wnt/β-catenin signaling pathway. SKI II also reduces the expression of c-Myc and cyclin D1, the downstream target genes of the Wnt signaling pathway. 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 inhibits the proliferation of HepG2 cells by blocking the Wnt/β-catenin signaling pathway. [1]<br>in vivo: SKI-II causes an irreversible inhibition of SK1 by inducing its lysosomal and/or proteasomal degradation. In the present study, SKI-II was administered 3-weekly i.p. to LDL-R-/- mice for 16 weeks at a dose previously demonstrated to reduce tumor growth in mice. Preliminary experiments revealed that a single administration of SKI-II produces a significant reduction of plasma S1P with the maximum (40%) observed 12 h after injection. [2]</p>
| Catalog Number | I003101 |
| CAS Number | 312636-16-1 |
| Synonyms | 4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenol |
| Molecular Formula | C₁₅H₁₁ClN₂OS |
| Purity | ≥95% |
| Target | S1P receptor |
| Solubility | DMSO: ＞ 34 mg/mL |
| Storage | Store at -20 C |
| IC50 | 78/45 μM (SK1/2) [2] |
| 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) |
| InChIKey | ZFGXZJKLOFCECI-UHFFFAOYSA-N |
| SMILES | C1=CC(=CC=C1C2=CSC(=N2)NC3=CC=C(C=C3)O)Cl |
| Reference | </br>1:Dual sphingosine kinase inhibitor SKI-II enhances sensitivity to 5-fluorouracil in hepatocellular carcinoma cells via suppression of osteopontin and FAK/IGF-1R signalling. Grbčić P, Tomljanović I, Klobučar M, Kraljević Pavelić S, Lučin K, Sedić M.Biochem Biophys Res Commun. 2017 Jun 10;487(4):782-788. doi: 10.1016/j.bbrc.2017.04.100. Epub 2017 Apr 19. PMID: 28433634 </br>2:SphK1 inhibitor SKI II inhibits the proliferation of human hepatoma HepG2 cells via the Wnt5A/β-catenin signaling pathway. Liu H, Zhang CX, Ma Y, He HW, Wang JP, Shao RG.Life Sci. 2016 Apr 15;151:23-9. doi: 10.1016/j.lfs.2016.02.098. Epub 2016 Mar 2. PMID: 26944438 </br>3:From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure-Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II). Aurelio L, Scullino CV, Pitman MR, Sexton A, Oliver V, Davies L, Rebello RJ, Furic L, Creek DJ, Pitson SM, Flynn BL.J Med Chem. 2016 Feb 11;59(3):965-84. doi: 10.1021/acs.jmedchem.5b01439. Epub 2016 Feb 3. PMID: 26780304 </br>4:SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo. Yang L, Weng W, Sun ZX, Fu XJ, Ma J, Zhuang WF.Biochem Biophys Res Commun. 2015 May 15;460(4):903-8. doi: 10.1016/j.bbrc.2015.03.114. Epub 2015 Mar 28. PMID: 25824043 </br>5:SKI-II–a sphingosine kinase 1 inhibitor–exacerbates atherosclerosis in low-density lipoprotein receptor-deficient (LDL-R-/-) mice on high cholesterol diet. Potì F, Ceglarek U, Burkhardt R, Simoni M, Nofer JR.Atherosclerosis. 2015 May;240(1):212-5. doi: 10.1016/j.atherosclerosis.2015.03.020. Epub 2015 Mar 16. PMID: 25801013 </br>6:A sphingosine kinase-1 inhibitor, SKI-II, induces growth inhibition and apoptosis in human gastric cancer cells. Li PH, Wu JX, Zheng JN, Pei DS.Asian Pac J Cancer Prev. 2014;15(23):10381-5. PMID: 25556479 Free Article</br>7:SKI-II reverses the chemoresistance of SGC7901/DDP gastric cancer cells. Liu Y, Zhu Z, Cai H, Liu Q, Zhou H, Zhu Z.Oncol Lett. 2014 Jul;8(1):367-373. Epub 2014 Apr 25. PMID: 24959278 Free PMC Article</br>8:Inhibition of dihydroceramide desaturase activity by the sphingosine kinase inhibitor SKI II. Cingolani F, Casasampere M, Sanllehí P, Casas J, Bujons J, Fabrias G.J Lipid Res. 2014 Aug;55(8):1711-20. doi: 10.1194/jlr.M049759. Epub 2014 May 29. PMID: 24875537 Free PMC Article</br>9:[Inhibitions of SphK1 inhibitor SKI II on cell cycle progression and cell invasion of hepatoma HepG2 cells]. Zhang CX, Liu H, Gong YY, He HW, Shao RG.Yao Xue Xue Bao. 2014 Feb;49(2):204-8. Chinese. PMID: 24761610 </br>10:Activation of transcription factor Nrf2 signalling by the sphingosine kinase inhibitor SKI-II is mediated by the formation of Keap1 dimers. Mercado N, Kizawa Y, Ueda K, Xiong Y, Kimura G, Moses A, Curtis JM, Ito K, Barnes PJ.PLoS One. 2014 Feb 5;9(2):e88168. doi: 10.1371/journal.pone.0088168. eCollection 2014. Erratum in: PLoS One. 2014;9(5):e97208. PMID: 24505412 Free PMC Article |
