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].
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
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
Click here for help
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)
Bioactivity Comments
Off-target inhibition of dihydroceramide desaturase-1 (DEGS1) by SKI II is primarily responsible for the compound's antiproliferative effects.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
delta 4-desaturase, sphingolipid 1 Hs Inhibitor Inhibition 6.5 pKi - 2
pKi 6.5 (Ki 3x10-7 M) [2]
sphingosine kinase 2 Hs Inhibitor Inhibition 5.1 pKi - 5
pKi 5.1 (Ki 7.9x10-6 M) [5]
sphingosine kinase 1 Hs Inhibitor Inhibition 4.8 pKi - 4
pKi 4.8 (Ki 1.6x10-5 M) [4]
sphingosine kinase 1 Primary target of this compound Hs Inhibitor Inhibition 6.3 pIC50 - 3
pIC50 6.3 (IC50 5x10-7 M) [3]
Description: Measured using a GST-hSPHK1 fusion protein