Cofactor Mimics as Selective Inhibitors of NAD-dependent Inosine Monophospate Dehydrogenase (IMPDH) - the Major Therapeutic Target
Krzysztof W. Pankiewicz, Steven E. Patterson, Paul L. Black, Hiremagalur N. Jayaram, Dipesh Risal, Barry M. Goldstein, Lieven J. Stuyver and Raymond F. Schinazi
Affiliation: Pharmasset, Inc., 1860 Montreal Road, Tucker, Atlanta, GA 30084, USA.
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 broadspectrum antiviral agent, which in combination with interferon-α 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.
Keywords: inosine monophospate dehydrogenase, imp dehydrogenase, purine nucleotides, mycophenolic mofetil
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