Design and synthesis of highly potent fumagillin analogues from homology modeling for a human MetAP-2

Bioorg Med Chem Lett. 2000 Jan 3;10(1):39-43. doi: 10.1016/s0960-894x(99)00577-6.

Abstract

New fumagillin analogues were designed through structure-based molecular modeling with a human methionine aminopeptidase-2. Among the fumagillin analogues, cinnamic acid ester derivative CKD-731 showed 1000-fold more potent proliferation inhibitory activity on endothelial cell than TNP-470.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Aminopeptidases / chemistry*
  • Angiogenesis Inhibitors / chemical synthesis*
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Cattle
  • Cell Line
  • Cinnamates / chemical synthesis
  • Cinnamates / pharmacology
  • Cyclohexanes
  • Drug Design
  • Epoxy Compounds / chemical synthesis
  • Epoxy Compounds / pharmacology
  • Fatty Acids, Unsaturated / chemical synthesis*
  • Fatty Acids, Unsaturated / pharmacology*
  • Growth Inhibitors / pharmacology
  • Humans
  • Leukemia P388 / pathology
  • Metalloendopeptidases / chemistry*
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
  • Sesquiterpenes
  • Structure-Activity Relationship

Substances

  • Angiogenesis Inhibitors
  • Cinnamates
  • Cyclohexanes
  • Epoxy Compounds
  • Fatty Acids, Unsaturated
  • Growth Inhibitors
  • Sesquiterpenes
  • CKD 731
  • fumagillin
  • Aminopeptidases
  • methionine aminopeptidase 2
  • Metalloendopeptidases