IDH1 / IDH2
A metabolic enzyme whose mutant form produces a molecule that scrambles how genes are read; blocking it slows brain tumours and leukaemias.
Mutant IDH produces the oncometabolite 2-hydroxyglutarate. Ivosidenib (IDH1) and enasidenib (IDH2) are approved in AML; ivosidenib in cholangiocarcinoma; vorasidenib (Voranigo, dual IDH1/2) in grade 2 IDH-mutant glioma (INDIGO, 2024), the first targeted therapy for low-grade glioma.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
In plain words · A metabolic enzyme whose mutant form produces a molecule that scrambles how genes are read; blocking it slows brain tumours and leukaemias.
- 1 · What it is
A metabolic enzyme whose mutant form produces a molecule that scrambles how genes are read; blocking it slows brain tumours and leukaemias.
- 2 · What goes wrong in cancer
Neomorphic enzyme activity; 2-HG inhibits TET and histone demethylases.
- 3 · How drugs use it
4 products aim at IDH1 / IDH2: small molecules. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Biology
Neomorphic enzyme activity; 2-HG inhibits TET and histone demethylases.
- Low-grade glioma (~80%)
- AML (~20%)
- Cholangiocarcinoma (~15%)
- Chondrosarcoma
How common it is, by cancer
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Glioma & glioblastoma | 70-80% | IDH1/2 mutation in grade 2-3 glioma | <10% in primary glioblastoma | cBioPortal (TCGA) |
| Acute myeloid leukaemia | 15-20% | IDH1 or IDH2 mutation | cBioPortal (TCGA) | |
| Biliary tract cancer | 10-20% | IDH1 mutation (intrahepatic) | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Enasidenib is the IDH2 counterpart of ivosidenib, approved in the US for relapsed disease but never approved in Europe after it failed to extend survival in a confirmatory trial.
Ivosidenib is a pill that blocks the mutant IDH1 enzyme, approved in bile duct cancer and in leukaemia.
Olutasidenib is a second IDH1 inhibitor for relapsed AML, with a higher response rate in its pivotal cohort than ivosidenib had in its own.
The first targeted therapy for low-grade brain tumours, delaying the need for radiation and chemotherapy by years.
Latest papers
topQuery for this target: (TITLE:"IDH1 / IDH2" OR ABSTRACT:"IDH1 / IDH2" OR TITLE:"IDH1" OR ABSTRACT:"IDH1" OR TITLE:"IDH2" OR ABSTRACT:"IDH2") 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 IDH1 / IDH2, not a curated reading list.
Pages like this
not linked directly; found by shared links- TargetMenin
Shares Differentiation syndrome, Epigenetic reprogramming, Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET), Acute myeloid leukaemia and the tag epigenetic.
- TargetEZH2
Shares Group trials by broken mechanism, not by organ or single mutation, Epigenetic reprogramming, Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET) and the tag epigenetic.
- TargetKRAS
Shares Glutamine addiction and the tag driver.
- TargetNPM1 mutation
Shares Timothy J. Ley, Epigenetic reprogramming, Acute myeloid leukaemia and the tag driver.
- TargetFGFR2
Shares Intrahepatic, perihilar, distal and gallbladder cancer, National Cancer Centre Singapore, Biliary tract cancer (cholangiocarcinoma) and the tag driver.
- TargetKMT2A (MLL) rearrangement
Shares Group trials by broken mechanism, not by organ or single mutation, Epigenetic reprogramming, Acute myeloid leukaemia and the tag driver.
- TargetHER2
Shares Intrahepatic, perihilar, distal and gallbladder cancer, The brain: barrier and sanctuary, Biliary tract cancer (cholangiocarcinoma) and the tag driver.
- TargetBRAF
Shares Biliary tract cancer (cholangiocarcinoma), Glioma & glioblastoma and the tag driver.