IMP dehydrogenase (IMPDH2)
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
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.
External identifiers
Biology
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.
- Activated lymphocytes
- Glioblastoma, small-cell lung cancer and other rapidly dividing tumours
Latest papers
topQuery 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.