Cofactor Mimics as Selective Inhibitors of NAD-dependent Inosine Monophospate Dehydrogenase (IMPDH) - the Major Therapeutic Target

Authors: Pankiewicz, Krzysztof W.; Patterson, Steven E.; Black, Paul L.; Jayaram, Hiremagalur N.; Risal, Dipesh; Goldstein, Barry M.; Stuyver, Lieven J.; Schinazi, Raymond F.

Source: Current Medicinal Chemistry, Volume 11, Number 7, April 2004 , pp. 887-900(14)

Publisher: Bentham Science Publishers

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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 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: imp dehydrogenase; inosine monophospate dehydrogenase; mycophenolic mofetil; purine nucleotides

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867043455648

Affiliations: Pharmasset, Inc., 1860 Montreal Road, Tucker, Atlanta, GA 30084, USA.

Publication date: April 1, 2004

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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