Discovery of novel sphingosine kinase 1 inhibitors

Bioorg Med Chem Lett. 2009 Nov 1;19(21):6119-21. doi: 10.1016/j.bmcl.2009.09.022. Epub 2009 Sep 10.

Abstract

Sphingosine kinase 1 (SK1) is an important enzyme that regulates the balance between ceramide and sphingosine-1-phosphate (S1P). Potent and novel SK1 inhibitors (6ag, 9ab and 12aa) have been discovered through a series of modifications of sphingosine (1), the substrate of this enzyme.

MeSH terms

  • Aminobutyrates / chemical synthesis
  • Aminobutyrates / chemistry*
  • Aminobutyrates / pharmacology
  • Cell Line, Tumor
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology
  • Homoserine / analogs & derivatives*
  • Homoserine / chemical synthesis
  • Homoserine / chemistry
  • Homoserine / pharmacology
  • Humans
  • Lysophospholipids / chemistry
  • Lysophospholipids / metabolism
  • Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Proline / analogs & derivatives*
  • Proline / chemical synthesis
  • Proline / chemistry
  • Proline / pharmacology
  • Sphingosine / analogs & derivatives
  • Sphingosine / chemistry
  • Sphingosine / metabolism

Substances

  • Aminobutyrates
  • Enzyme Inhibitors
  • Lysophospholipids
  • sphingosine 1-phosphate
  • Homoserine
  • Proline
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase
  • Sphingosine