{"entity":{"id":"idh-inhibitors","kind":"technology","name":"IDH inhibitors","aka":[],"tldr":"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.","status":"approved","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Isocitrate_dehydrogenase","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Isocitrate_dehydrogenase"}],"tags":[],"related":[],"cancers":["aml","cholangiocarcinoma","glioblastoma","chondrosarcoma"],"sections":["targeted-therapy"],"technologies":[],"targets":[],"drugs":["ivosidenib","enasidenib","olutasidenib","vorasidenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Allosteric inhibitors lock the mutant enzyme in an inactive state, lowering 2-hydroxyglutarate and restoring differentiation.","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"],"since":2018},"route":"/technologies/idh-inhibitors/","neighbours":{"cancer":[{"id":"aml","kind":"cancer","name":"Acute myeloid leukaemia","route":"/cancers/aml/"},{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"chondrosarcoma","kind":"cancer","name":"Chondrosarcoma","route":"/cancers/chondrosarcoma/"},{"id":"glioblastoma","kind":"cancer","name":"Glioma & glioblastoma","route":"/cancers/glioblastoma/"}],"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"drug":[{"id":"enasidenib","kind":"drug","name":"Enasidenib","route":"/drugs/enasidenib/"},{"id":"ivosidenib","kind":"drug","name":"Ivosidenib","route":"/drugs/ivosidenib/"},{"id":"olutasidenib","kind":"drug","name":"Olutasidenib","route":"/drugs/olutasidenib/"},{"id":"vorasidenib","kind":"drug","name":"Vorasidenib","route":"/drugs/vorasidenib/"}],"trial":[{"id":"agile","kind":"trial","name":"AGILE","route":"/trials/agile/"},{"id":"nct05876754","kind":"trial","name":"An Early Access Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma","route":"/trials/nct05876754/"},{"id":"nct07282262","kind":"trial","name":"An Exploratory Study on the Use of Ivosidenib for the Precise Treatment of Advanced Biliary Tract Malignancies With IDH1 Mutations in the Later Line of Therapy.","route":"/trials/nct07282262/"},{"id":"nct05907057","kind":"trial","name":"An Open-label Phase 3b Study of Ivosidenib in Combination With Azacitidine in Adult Patients Newly Diagnosed With IDH1m Acute Myeloid Leukemia (AML) Ineligible for Intensive Induction Chemotherapy.","route":"/trials/nct05907057/"},{"id":"beat-aml-master-trial","kind":"trial","name":"Beat AML Master Trial","route":"/trials/beat-aml-master-trial/"},{"id":"claridhy","kind":"trial","name":"ClarIDHy","route":"/trials/claridhy/"},{"id":"indigo","kind":"trial","name":"INDIGO","route":"/trials/indigo/"},{"id":"nct07745296","kind":"trial","name":"Investigating Precision Medicine in the Adjuvant Setting in Biliary Tract Cancer","route":"/trials/nct07745296/"},{"id":"nct06127407","kind":"trial","name":"Ivosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen","route":"/trials/nct06127407/"},{"id":"nct06161974","kind":"trial","name":"Study of Olutasidenib and Temozolomide in HGG","route":"/trials/nct06161974/"}],"technology":[{"id":"epigenetic-drugs","kind":"technology","name":"Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)","route":"/technologies/epigenetic-drugs/"}],"term":[{"id":"epigenetic-progenitor-theory","kind":"term","name":"Epigenetic progenitor theory: cancer without a first mutation","route":"/terms/epigenetic-progenitor-theory/"},{"id":"metabolic-theory-of-cancer","kind":"term","name":"Metabolic theory of cancer: from Warburg to oncometabolites","route":"/terms/metabolic-theory-of-cancer/"}]}}