SKI II   Click here for help

GtoPdb Ligand ID: 6041

Synonyms: SKI 2 | SKI-II
PDB Ligand
Compound class: Synthetic organic
Comment: The discovery of this selective sphingosine kinase inhibitor is described in [3], where it is called compound II.
The above article cites [8] for the creation of the human sphingosine kinase protein used in their kinase assay. BLAST searches using the accession numbers in this article indicate the kinase assay was performed using the SPHK1 isozyme. SKI II exhibits some selectivity toward SK2 as a kinase inhibitor (Ki for SK2 = 7.9 μM vs. SK1 = 16 μM) [3]. It is a more powerful promoter of SK1-degradation than of SK2-degradation [7].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 2
Hydrogen bond donors 2
Rotatable bonds 3
Topological polar surface area 73.39
Molecular weight 302.03
XLogP 4.29
No. Lipinski's rules broken 0
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Canonical SMILES Oc1ccc(cc1)Nc1scc(n1)c1ccc(cc1)Cl
Isomeric SMILES Oc1ccc(cc1)Nc1scc(n1)c1ccc(cc1)Cl
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)
1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011)
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]
2. Cingolani F, Casasampere M, Sanllehí P, Casas J, Bujons J, Fabrias G. (2014)
Inhibition of dihydroceramide desaturase activity by the sphingosine kinase inhibitor SKI II.
J Lipid Res, 55 (8): 1711-20. [PMID:24875537]
3. French KJ, Schrecengost RS, Lee BD, Zhuang Y, Smith SN, Eberly JL, Yun JK, Smith CD. (2003)
Discovery and evaluation of inhibitors of human sphingosine kinase.
Cancer Res, 63 (18): 5962-9. [PMID:14522923]
4. French KJ, Zhuang Y, Maines LW, Gao P, Wang W, Beljanski V, Upson JJ, Green CL, Keller SN, Smith CD. (2010)
Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2.
J Pharmacol Exp Ther, 333 (1): 129-39. [PMID:20061445]
5. Gao P, Peterson YK, Smith RA, Smith CD. (2012)
Characterization of isoenzyme-selective inhibitors of human sphingosine kinases.
PLoS ONE, 7 (9): e44543. [PMID:22970244]
6. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013)
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
Biochem J, 451 (2): 313-28. [PMID:23398362]
7. Loveridge C, Tonelli F, Leclercq T, Lim KG, Long JS, Berdyshev E, Tate RJ, Natarajan V, Pitson SM, Pyne NJ et al.. (2010)
The sphingosine kinase 1 inhibitor 2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole induces proteasomal degradation of sphingosine kinase 1 in mammalian cells.
J Biol Chem, 285 (50): 38841-52. [PMID:20926375]
8. Pitson SM, D'andrea RJ, Vandeleur L, Moretti PA, Xia P, Gamble JR, Vadas MA, Wattenberg BW. (2000)
Human sphingosine kinase: purification, molecular cloning and characterization of the native and recombinant enzymes.
Biochem J, 350 Pt 2: 429-41. [PMID:10947957]