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IMPDH is the bottleneck enzyme for making guanine nucleotides; mycophenolate blocks it to hold back the donor T cells that cause graft-versus-host disease after stem cell transplantation, and the enzyme is over-expressed in fast-growing tumours.
Inosine monophosphate dehydrogenase catalyses the rate-limiting step of guanine nucleotide synthesis, and the type 2 isoform is induced in proliferating lymphocytes and in many cancers. Mycophenolate mofetil, a prodrug of the IMPDH inhibitor mycophenolic acid, is used with a calcineurin inhibitor to prevent graft-versus-host disease after allogeneic stem cell transplantation, and IMPDH is also the target of the old antileukaemic drug tiazofurin and part of the action of ribavirin. Because glioblastoma, small-cell lung cancer and other tumours depend on IMPDH2 for nucleotide supply, repurposing mycophenolate as an anticancer agent is in early trials.
In plain words · IMPDH is the bottleneck enzyme for making guanine nucleotides; mycophenolate blocks it to hold back the donor T cells that cause graft-versus-host disease after stem cell transplantation, and the enzyme is over-expressed in fast-growing tumours.
IMPDH is the bottleneck enzyme for making guanine nucleotides; mycophenolate blocks it to hold back the donor T cells that cause graft-versus-host disease after stem cell transplantation, and the enzyme is over-expressed in fast-growing tumours.
A tetrameric NAD-dependent dehydrogenase that oxidises IMP to XMP; lymphocytes rely on this de novo route because they lack an efficient guanine salvage pathway.
No product in this corpus aims at IMP dehydrogenase (IMPDH2) yet. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
First described 1988. Earliest sequence paper UniProt cites for the protein: Collart F.R. et al, J. Biol. Chem, 1988, "Cloning and sequence analysis of the human and Chinese hamster inosine-5'-monophosphate dehydrogenase cDNAs". Source.
A tetrameric NAD-dependent dehydrogenase that oxidises IMP to XMP; lymphocytes rely on this de novo route because they lack an efficient guanine salvage pathway.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Prostate cancer | host% | Host enzyme in normal and malignant prostate; finasteride and dutasteride were tested for prevention, not as a tumour marker | cancer.gov |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Query for this target: (TITLE:"IMP dehydrogenase" OR ABSTRACT:"IMP dehydrogenase" OR TITLE:"IMPDH2" OR ABSTRACT:"IMPDH2") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about IMP dehydrogenase (IMPDH2), not a curated reading list.