Inosine 5'-monophosphate
dehydrogenase (IMPDH) represents an attractive target for the development of
anticancer agents; however, there are no drugs aimed at this target for the treatment of
cancer currently available on the market.
Tiazofurin, a potent IMPDH inhibitor, reached clinical trials with Orphan Drug status for the treatment of patients in
blast crisis of
chronic myelogenous leukemia (CML); however, it was considered too toxic for application against other
malignancies and no development has been reported for this
drug since 2002. Formulations of
mycophenolic acid, another potent inhibitor of IMPDH, are currently used for the prevention of rejection following
transplantation, and against
autoimmune diseases. More recently, numerous studies have demonstrated the potential of
mycophenolic acid as an
anticancer agent, with a phase I clinical trial in patients with advanced
multiple myeloma ongoing. Furthermore, synergy between imantinib and
mycophenolic acid in CML treatments has also been reported. Related compounds such as mycophenolic
adenine dinucleotides, along with second-generation analogs, are undergoing preclinical evaluation, while another inhibitor of IMPDH,
AVN-944, is currently in phase I clinical trials to investigate the treatment of
hematological malignancies. This article reviews recent applications of IMPDH inhibitors as
anticancer agents, and highlights the progress that has been made in this field.