Inhibition of Orotidine-5'-monophosphate decarboxylase - Discoveries and lessons

Orotidine-5'-monophosphate decarboxylase (ODCase) is one of most proficient enzymes, and this enzyme catalyzes the decarboxylation of orotidine-5'- monophosphate (OMP) to uridine-5'-monophosphate (UMP). A number of C6-substituted uridine derivatives are designed to investigate the mechanism of decarboxylation by this enzyme. In this process, novel reactions and mechanisms were uncovered for this decarboxylase. This led to the discovery of novel ODCase inhibitors and their biological activities. Medicinal chemistry of these novel inhibitors of ODCase in the context of its catalytic mechanism, and therapeutics development will be discussed.