Polyglutamation of methotrexate: Is Methotrexate a prodrug?

Abstract

The discovery of the polyglutamation process has complicated, but enriched, our understanding of the manner in which antimetabolites selectively kill tumor cells. It has focused our attention on the enzyme folylpolyglutamyl synthetase and has heightened the importance of gaining a clearer understanding of normal folate physiology and the effects of drug treatment on circulating and intracellular folates. With this new appreciation for the metabolic pathways of intracellular folates, it will be possible to design more effective treatment regimens and better antifolate agents.