# IDH inhibitors

Source: https://onco.cc/technologies/idh-inhibitors/  
OnCo record `idh-inhibitors` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Pills that block mutant IDH1 or IDH2 enzymes, which flood cells with a metabolite that blocks maturation; approved in leukaemia, bile duct cancer and low-grade glioma.

## Summary

Mutations in isocitrate dehydrogenase 1 and 2 produce the oncometabolite 2-hydroxyglutarate, which blocks cell differentiation through epigenetic enzymes. Enasidenib (IDH2, 2017) and ivosidenib (IDH1, 2018) were approved in acute myeloid leukaemia, ivosidenib later in cholangiocarcinoma, olutasidenib in AML, and vorasidenib, which penetrates the brain, delayed progression of IDH-mutant low-grade glioma and was approved in 2024. Differentiation syndrome and resistance through second-site mutations are the class issues.

## Fields

- Kind: Technology
- Status: approved
- Last checked: 2026-09-04
- Principle: Allosteric inhibitors lock the mutant enzyme in an inactive state, lowering 2-hydroxyglutarate and restoring differentiation.
- Since: 2018
- Strengths: Oral, well tolerated; First targeted therapy for IDH-mutant glioma; Approved across leukaemia and solid tumours
- Limitations: Differentiation syndrome; Isoform switching and second-site resistance; Responses in solid tumours are cytostatic

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Isocitrate_dehydrogenase
- Wikipedia: https://en.wikipedia.org/wiki/Isocitrate_dehydrogenase

## Connected records

- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/)
- fronts: [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- drugs: [Enasidenib](https://onco.cc/drugs/enasidenib/), [Ivosidenib](https://onco.cc/drugs/ivosidenib/), [Olutasidenib](https://onco.cc/drugs/olutasidenib/), [Vorasidenib](https://onco.cc/drugs/vorasidenib/)

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