Cofactor mimics as selective inhibitors of NAD-dependent inosine monophosphate dehydrogenase (IMPDH)--the major therapeutic target

Curr Med Chem. 2004 Apr;11(7):887-900. doi: 10.2174/0929867043455648.

Abstract

IMP dehydrogenase, the key enzyme in de novo synthesis of purine nucleotides, is an important therapeutic target. Three inhibitors of IMP dehydrogenase reached the market; ribavirin (Rebetol) a broad-spectrum antiviral agent, which in combination with interferon-alpha is now used for treatment of hepatitis C virus infections, mizoribine (Bredinin) and mycophenolic mofetil (CellCept) have been introduced as immunosuppressants. Numerous novel inhibitors are under development. This review describes recent progress in the development of new drugs based on inhibition of IMP dehydrogenase.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Catalysis
  • Enzyme Inhibitors* / chemistry
  • Enzyme Inhibitors* / pharmacology
  • Enzyme Inhibitors* / therapeutic use
  • Humans
  • IMP Dehydrogenase / antagonists & inhibitors*
  • Molecular Mimicry / physiology*
  • Molecular Structure
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacology
  • NAD / chemistry*
  • Ribavirin / analogs & derivatives*
  • Ribavirin / pharmacology
  • Ribonucleosides / pharmacology

Substances

  • Enzyme Inhibitors
  • Ribonucleosides
  • NAD
  • Ribavirin
  • mizoribine
  • IMP Dehydrogenase
  • Mycophenolic Acid
  • tiazofurin