IMPDH2 belongs to the IMPDH/GMPR family and is one of two isoforms of IMP dehydrogenase found in humans . The other isoform, IMPDH1, is generally constitutively expressed, whereas IMPDH2 is inducible during cellular proliferation and transformation . The two isoforms share 84% sequence identity but are distinctly regulated .
IMPDH2 plays a pivotal role in maintaining the cellular pools of guanine nucleotides, which are essential for DNA and RNA synthesis . The enzyme’s activity is crucial for rapidly proliferating cells, such as lymphocytes and tumor cells . Due to its central role in nucleotide biosynthesis, IMPDH2 is a validated target for several therapeutic applications, including antiviral, antiparasitic, antimicrobial, antileukemic, and immunosuppressive treatments .
Recombinant human IMPDH2 is produced using various expression systems, including E. coli and baculovirus-infected insect cells . The recombinant enzyme retains its catalytic activity and is used in research to study its function and to screen for potential inhibitors . The enzyme’s activity is measured by its ability to convert IMP to XMP, with specific activity values provided under defined assay conditions .
IMPDH2 inhibitors, such as mycophenolic acid (MPA) and ribavirin, are used to treat a wide range of diseases . MPA, for example, is an immunosuppressive agent used to prevent organ transplant rejection and to treat autoimmune diseases . The inhibition of IMPDH2 leads to a decrease in guanine nucleotide levels, which in turn disrupts nucleic acid synthesis in proliferating cells .