SLM6071469   Click here for help

GtoPdb Ligand ID: 10641

Synonyms: compound 10 [PMID: 31895563] [1]
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Compound 10 is an inhibitor of sphingosine kinase 2 [1]. This compound exploits a novel side cavity on the kinase to provide enhanced potency and selectivity. The PubChem entry for this compound originated via SureChEMBL patent extraction, and is derived from patent WO2017172989A1 from researchers at Virginia Tech [2].
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 4
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 101.26
Molecular weight 499.14
XLogP 6.43
No. Lipinski's rules broken 1
Click here for help
Canonical SMILES NC(=N)N1CCC[C@H]1c1onc(n1)c1ccc(c(c1)C(F)(F)F)OCc1ccc(cc1)C(F)(F)F
Isomeric SMILES NC(=N)N1CCC[C@H]1c1onc(n1)c1ccc(c(c1)C(F)(F)F)OCc1ccc(cc1)C(F)(F)F
InChI InChI=1S/C22H19F6N5O2/c23-21(24,25)14-6-3-12(4-7-14)11-34-17-8-5-13(10-15(17)22(26,27)28)18-31-19(35-32-18)16-2-1-9-33(16)20(29)30/h3-8,10,16H,1-2,9,11H2,(H3,29,30)/t16-/m0/s1
Bioactivity Comments
Compound 10 is >70-fold selective for SphK2 over SphK1 in vitro [1]. It is active in vivo (in C57BL/6 male mice via intraperitoneal administration), using blood S1P levels as a pharmacodynamic marker for SphK2 inhibition.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
sphingosine kinase 2 Hs Inhibitor Inhibition 7.1 pKi - 1
pKi 7.1 (Ki 8.9x10-8 M) [1]
Description: Biochemical assay using recombinant human SphK2.
sphingosine kinase 1 Hs Inhibitor Inhibition 5.2 pKi - 1
pKi 5.2 (Ki 6.5x10-6 M) [1]