Identification of type 1 inosine monophosphate dehydrogenase as an antiangiogenic drug target

J Med Chem. 2006 May 4;49(9):2677-80. doi: 10.1021/jm051225t.

Abstract

To rapidly discover clinically useful angiogenesis inhibitors, we created and screened a library of existing drugs for inhibition of endothelial cell proliferation. Mycophenolic acid (MPA), an immunosuppressive drug, was found to potently inhibit endothelial cell proliferation in vitro and block tumor-induced angiogenesis in vivo. Using RNA interference, we found that knockdown of one of the two known isoforms of inosine monophosphate dehydrogenase (IMPDH-1) is sufficient to cause endothelial cell cycle arrest.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / chemistry*
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • IMP Dehydrogenase / antagonists & inhibitors*
  • IMP Dehydrogenase / genetics
  • IMP Dehydrogenase / metabolism*
  • Mice
  • Molecular Structure
  • Mycophenolic Acid / chemistry*
  • Mycophenolic Acid / pharmacology*
  • Neoplasms / blood supply
  • Neoplasms / pathology
  • RNA Interference
  • Umbilical Cord / drug effects

Substances

  • Angiogenesis Inhibitors
  • Enzyme Inhibitors
  • IMP Dehydrogenase
  • Mycophenolic Acid