IDH1 Mutation ( Gliomas, prostate cancer, neuroblastoma, acute myeloid leukemia, cholangiocarcinoma)
IDH1 The full name is soluble isocitrate dehydrogenase1。 Isocitrate dehydrogenase (IDH) is the rate limiting enzyme in the tricarboxylic acid cycle, catalyzing the production of citric acidα Ketoglutarate (α - ketoglutarate,α - KG), whose family includes IDH1、IDH2 AndIDH3 Three members. The first research found thatIDH1 The mutation is closely related to glioma, and later it was found that its mutation is associated with prostate, paraganglioma, andIDH1/2 Mutation is associated with acute myeloid leukemia. Its carcinogenic mechanism is mutationIDH Can beα- Ketoglutaric acid is converted into2- Hydroxyglutaric acid, and the latter can inhibit the targets of the former, causing abnormalities in these targets and leading to cancer.
ByIDH1 AndIDH2 Abnormalities caused by genetic mutationsNADP +-dependent Heterotopic citrate dehydrogenase occurs in many types of malignant gliomas, and these mutations can explain the evolution of malignant glioblastoma from low-grade gliomas.
Targeted therapeutic drugs：
2021 Year by yearFDA ApprovedIvosidenib（Tibsovo，IVO，AG-120） Indications for the treatment of those who have received frontline treatment plansIDH1 Patients with mutation positive cholangiocarcinoma. AGI-5198 It is the first efficient and selective oneIDH1 R132H/R132C Mutant inhibitors.
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