Cofactor mimics as selective inhibitors of NAD-dependent inosine monophosphate dehydrogenase (IMPDH)--the major therapeutic target.
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.
Pankiewicz
Krzysztof W
KW
Pharmasset, Inc., Atlanta, GA 30084, USA. kpankiewicz@pharmasset.com
Patterson
Steven E
SE
Black
Paul L
PL
Jayaram
Hiremagalur N
HN
Risal
Dipesh
D
Goldstein
Barry M
BM
Stuyver
Lieven J
LJ
Schinazi
Raymond F
RF
D002384:Catalysis; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D018716:Molecular Mimicry / Q000502:physiology*; D015394:Molecular Structure; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D009243:NAD / Q000737:chemistry*; D012254:Ribavirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012263:Ribonucleosides / Q000494:pharmacology
D004791:Enzyme Inhibitors; D012263:Ribonucleosides; D009243:NAD; D012254:Ribavirin; C010052:mizoribine; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid; C033706:tiazofurin