Design of inhibitors of ODCase.

ABSTRACT

ODCase is a highly proficient enzyme responsible for the decarboxylation of orotidine monophosphate to generate uridine monophosphate. ODCase has attracted early attention due to its interesting mechanism of catalysis. In order to exploit therapeutic advantages due to the inhibition of ODCase, one must have selective inhibitors of this enzyme from the pathogen, or a dysregulated molecular mechanism involving ODCase. ODCase inhibitors have potential applications as anticancer agents, antiviral agents, antimalarial agents and potentially act against other parasitic diseases. A variety of C6-substituted uridine monophosphate derivatives have shown excellent inhibition of ODCase. 6-iodouridine is a potent inhibitor of the malaria parasite, and its monophosphate form covalently inhibits ODCase. A variety of inhibitors of ODCase with potential applications as therapeutic agents are discussed in this review.