title: Cofactor mimics as selective inhibitors of NAD-dependent inosine monophosphate dehydrogenase (IMPDH)--the major therapeutic target.
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.
authors.affiliation: Pharmasset, Inc., Atlanta, GA 30084, USA. kpankiewicz@pharmasset.com
authors.forename: Krzysztof W
authors.initials: KW
authors.lastname: Pankiewicz
authors.forename: Steven E
authors.initials: SE
authors.lastname: Patterson
authors.forename: Paul L
authors.initials: PL
authors.lastname: Black
authors.forename: Hiremagalur N
authors.initials: HN
authors.lastname: Jayaram
authors.forename: Dipesh
authors.initials: D
authors.lastname: Risal
authors.forename: Barry M
authors.initials: BM
authors.lastname: Goldstein
authors.forename: Lieven J
authors.initials: LJ
authors.lastname: Stuyver
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D012263:Ribonucleosides; D009243:NAD; D012254:Ribavirin; C010052:mizoribine; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid; C033706:tiazofurin