Inosine monophosphate dehydrogenase (IMPDH) as a target in drug discovery.

Qingning Shu, Vasu Nair

Journal: Medicinal research reviews 2008;28(2):219-32

PMID: 17480004

Abstract

Inosine monophosphate dehydrogenase (IMPDH) is a key enzyme of de novo purine nucleotide biosynthesis and is viewed as an important target in the quest for discovery of drugs in the antiviral, antibacterial and anticancer therapeutic areas. This review focuses on the medicinal chemistry, drug discovery and chemical biology of IMPDH. Examples of IMP and cofactor site-directed inhibitors, allosteric inhibitors and isoform-selective inhibitors are presented. Comparison of IMPDHs from different organisms is also made to facilitate the design of species-selective IMPDH inhibitors for drug discovery. Special emphasis in the review is placed on IMPDH from Mycobacterium tuberculosis.

Address: The Center for Drug Discovery and the Department of Pharmaceutical and Biomedical Sciences, R. C. Wilson PH, University of Georgia, Athens, Georgia 30602, USA.

DOI: 10.1002/med.20104

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MeSH Terms: Allosteric Site, Amino Acid Sequence, Binding Sites, Drug Design, Humans, IMP Dehydrogenase, Isoenzymes, Ligands, Models, Molecular, Molecular Sequence Data, Mycobacterium tuberculosis, NAD, Sequence Alignment