Inosine-5-monophosphate dehydrogenase 1 (IMPDH1)

Inosine-5-monophosphate dehydrogenase 1 (IMPDH1) is a key rate-limiting enzyme in the de novo synthesis of guanine nucleotides, catalyzing the nicotinamide adenine dinucleotide (NAD+)-dependent oxidation of inosine monophosphate (IMP) to xanthosine monophosphate (XMP) [8, 11, 14]. This enzymatic step is essential for maintaining the intracellular pools of GTP and dGTP required for DNA and RNA synthesis, signal transduction, and energy metabolism [13, 16, 18]. While IMPDH1 is constitutively expressed in most tissues as a housekeeping isoform, it is particularly critical in the retina, where specific mutations lead to severe visual impairments such as retinitis pigmentosa 10 (RP10) and Leber congenital amaurosis 11 (LCA11) [3, 8, 15]. Pharmacologically, IMPDH1 is a major target for immunosuppressive, antiviral, and anticancer therapies [8, 11, 16]. Drugs such as mycophenolic acid and ribavirin inhibit its activity, thereby depleting guanine nucleotide levels and selectively halting the proliferation of rapidly dividing cells like activated lymphocytes and certain tumor cells [16, 18, 20]. Beyond its catalytic role, IMPDH1 also exhibits moonlighting functions, including the ability to bind single-stranded nucleic acids, which may play a role in regulating gene expression or RNA metabolism [1, 6, 8].

Other names

IMPD 1IMPD1IMP dehydrogenase 1IMPDH 1IMPDH-IsWSS2608LCA11

Inhibition of IMPDH activity leading to depletion of guanine nucleotide pools and suppression of cell proliferation.