IMPDH2

IMPDH2 (inosine-5'-monophosphate dehydrogenase 2) is a rate-limiting enzyme in de novo guanine nucleotide biosynthesis that catalyzes the NAD-dependent conversion of inosine monophosphate (IMP) to xanthosine monophosphate (XMP), thereby maintaining intracellular guanine nucleotide pools required for DNA synthesis, RNA synthesis, signal transduction, and cellular proliferation^[1][2]. The enzyme occupies a central position in purine metabolism and directly regulates GTP availability, linking nucleotide biosynthesis to cell growth and metabolic demand^[1][2]. Mechanistically, increased IMPDH2 expression is associated with proliferating cells and neoplastic tissues, where enhanced guanine nucleotide production supports tumor growth and cellular expansion^[3][4]. In disease contexts, dysregulated IMPDH2 expression has been reported across multiple cancer models, and elevated IMPDH2 activity has been linked to malignant progression, therapy response, and metabolic reprogramming dependent on GTP synthesis^[4][5]. Compared with the closely related isoform IMPDH1, which shares approximately 84% sequence identity and is generally considered a constitutively expressed housekeeping enzyme, IMPDH2 is preferentially upregulated during proliferation and tumorigenesis, making it the dominant isoform in many rapidly growing cells^[3][6]. This isoform-specific regulation provides an important rationale for experimental targeting of IMPDH2 in cancer and immunology research^[3][5]. For research applications, IMPDH inhibitors such as mycophenolic acid (MPA) suppress guanine nucleotide synthesis through direct enzyme inhibition and are widely used to investigate nucleotide metabolism, cell-cycle regulation, immune-cell activation, and IMPDH-dependent signaling pathways^[7][8].