Inhibitors of inosine monophosphate dehydrogenase as potential chemotherapeutic agents

Abstract

Inosine monophosphate dehydrogenase (IMPDH), an NAD-dependent enzyme which controls de novo synthesis of purine nucleotides, is an important target for the development of chemotherapeutic agents. The concentration of IMPDH was found to increase in tumour cells and activated lymphocytes. Thus, inhibition of IMPDH would result in anticancer and immunosuppressive activities. Since there is an increased demand for purine nucleotides in virus infected cells needed for RNA and DNA synthesis, inhibition of IMPDH may also lead to antiviral activity. IMPDHs from bacteria, parasites and mammalian sources differ significantly. Such differences can be exploited for the development of antibacterial or antiparasitic agents. Recent progress in revealing the molecular structure, mechanism of action and interactions of the enzyme with the co-factor and inhibitors provided a new stimulus for the development of novel agents targeted against IMPDH. This review covers both academic and industrial studies aimed at inhibition of IMPDH.