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

Inosine 5′-monophosphate dehydrogenase 1 and 2 (IMPDH1/IMPDH2) are NAD^+-dependent oxidoreductases that catalyze the conversion of inosine 5′-monophosphate (IMP) to xanthosine 5′-monophosphate (XMP), the rate-limiting step in *de novo* biosynthesis of guanine nucleotides. They are essential regulators of cellular guanine nucleotide pools, impacting DNA/RNA synthesis, energy transfer, signal transduction, and cell proliferation. IMPDH2 is particularly upregulated in cancer and is targeted by multiple antiviral, antitumor, antimicrobial, and immunosuppressive drugs. In addition to their enzymatic activity, these proteins have important alternate (moonlighting) functions, including transcriptional regulation and interaction with cellular structures. Mutations in IMPDH1 cause retinal degeneration, while mutations in IMPDH2 are implicated in neurodevelopmental disorders. Isoform- and species-selective inhibitors offer promise for targeted therapies with potentially reduced side effects.

Other names

IMP dehydrogenaseIMPDHinosine monophosphate dehydrogenaseIMPDH1 proteinIMPDH2 protein

Competitive inhibition of catalytic site, Cofactor-directed inhibition, Allosteric inhibition, Isoform-selective inhibition, Site-directed inhibition targeting substrate/cofactor binding