IDH inhibitors
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.
Overview
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.
How it works
Allosteric inhibitors lock the mutant enzyme in an inactive state, lowering 2-hydroxyglutarate and restoring differentiation.
- Oral, well tolerated
- First targeted therapy for IDH-mutant glioma
- Approved across leukaemia and solid tumours
- Differentiation syndrome
- Isoform switching and second-site resistance
- Responses in solid tumours are cytostatic
Latest papers
topQuery for this technology: (TITLE:"IDH inhibitors" OR ABSTRACT:"IDH inhibitors") 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 IDH inhibitors, not a curated reading list.
Similar pages
not linked directly; found by shared links- PathwayMutant IDH / 2-hydroxyglutarate
Shares Enasidenib, Olutasidenib, Ivosidenib, Vorasidenib.
- CompanyRigel Pharmaceuticals
Shares Olutasidenib, Acute myeloid leukaemia.
- TermDifferentiation syndrome
Shares Enasidenib, Olutasidenib, Ivosidenib, Acute myeloid leukaemia.
- CompanyServier
Shares Ivosidenib, Vorasidenib, Biliary tract cancer (cholangiocarcinoma), Glioma & glioblastoma.
- TrialClarIDHy
Shares Ivosidenib, Biliary tract cancer (cholangiocarcinoma).
- CompanyHangzhou Hanx Biopharmaceuticals
Shares Biliary tract cancer (cholangiocarcinoma), Glioma & glioblastoma.
- CompanyBasilea Pharmaceutica
Shares Biliary tract cancer (cholangiocarcinoma), Glioma & glioblastoma.
- TargetIDH1 / IDH2
Shares Enasidenib, Olutasidenib, Ivosidenib, Vorasidenib.