Inosine 5′-monophosphate dehydrogenase 1 and Inosine 5′-monophosphate dehydrogenase 2 (IMPDH1, IMPDH2)

Inosine 5′-monophosphate dehydrogenase (IMPDH) is a key enzyme in purine nucleotide metabolism, catalyzing the NAD-dependent oxidation of inosine 5'-monophosphate (IMP) to xanthosine 5'-monophosphate (XMP), which is the rate-limiting step in the de novo biosynthesis of guanine nucleotides[1][3][6]. IMPDH exists in two main human isoforms—IMPDH1 and IMPDH2—with IMPDH2 especially upregulated in proliferating and neoplastic cells, making it a major drug target in oncology and immunosuppression[2][4]. Through regulation of guanine nucleotides, IMPDH controls processes essential for cell growth, division, and immune responses. The enzyme also has structural features (Bateman domain) that endow additional regulatory or "moonlighting" roles, including RNA binding and involvement in transcriptional control[3][4]. Selective inhibition of IMPDH leads to cytostatic effects, which are exploited in therapies for transplantation, autoimmune diseases, cancer, and viral infections, but therapeutic use is associated with immunosuppression and other safety challenges[1][5].

Other names

IMPDH (general for either isoform)IMP dehydrogenasetype I IMP dehydrogenase (IMPDH1)type II IMP dehydrogenase (IMPDH2)

Competitive inhibition of IMPDH active site (e.g., mycophenolic acid, mizoribine) Nucleotide analogues acting as substrates or inhibitors (e.g., ribavirin) NAD analogue binding/interference (e.g., tiazofurin metabolite TAD/SAD) Depletion of intracellular guanine nucleotide pools leading to impaired cell growth and proliferation