isocitrate dehydrogenase 1

Overview

Isocitrate dehydrogenase 1 (IDH1) is a metabolic enzyme that functions in the cytosol and peroxisomes as part of cellular intermediary metabolism. It catalyzes the conversion of isocitrate to alpha-ketoglutarate, linking IDH1 to the tricarboxylic acid cycle–related metabolic network and to broader redox and biosynthetic processes. Because of this central metabolic role, IDH1 has been studied not only as a housekeeping enzyme but also as a biologically and clinically relevant target in cancer and other disease contexts.

In recent biomedical research, IDH1 has attracted attention as a target for both mutant and wild-type enzyme biology. The studies provided here highlight IDH1 involvement in glioblastoma imaging, chemoresistance in intrahepatic cholangiocarcinoma, prognostic stratification in acute myeloid leukemia, targeted therapy in biliary tract cancer, and immune-metabolic regulation in Alzheimer’s disease. These reports collectively underscore IDH1 as a molecule at the intersection of metabolism, tumor biology, and therapeutic targeting.

Focus of Latest Publications

Recent publications have examined isocitrate dehydrogenase 1 (IDH1) as both a diagnostic biomarker and a therapeutic target across several disease contexts. In glioblastoma, IDH1 status was incorporated into a patient-specific reaction-diffusion modeling framework alongside standard MRI and immunohistochemical markers such as Ki-67, with the model showing improved agreement between simulated and observed tumor extent and generating estimates of microscopic infiltration beyond visible MRI margins. Another glioblastoma study developed the fluorescent probe QM-SO3H to target wild-type IDH1 for intraoperative imaging; in an orthotopic xenograft model, the probe penetrated the impaired blood–brain barrier, delineated tumor boundaries, guided complete resection, and detected microtumors smaller than 1 mm.

IDH1 has also been explored in neurodegenerative disease. In Alzheimer’s disease, IDH1 was reported to be upregulated in microglia from patients and 5×FAD mice, where it promoted abnormal citrate metabolism, impaired mitochondrial TCA cycle function, and contributed to neuroinflammation and disease-related pathology. Using structure-based screening and co-crystallization analysis, investigators identified kinsenoside as a selective competitive inhibitor of IDH1 that binds the isocitrate-binding pocket. In 5×FAD mice, IDH1 inhibition restored citrate distribution and metabolic homeostasis, reduced Beta amyloid deposition, attenuated neuroinflammation, and improved cognitive performance.

In oncology, IDH1 was highlighted as a clinically relevant molecular alteration in biliary tract cancer, where comprehensive profiling has identified IDH1 mutations among actionable targets for precision therapy. A separate study in intrahepatic cholangiocarcinoma focused on wild-type IDH1 as a mediator of gemcitabine resistance. Using a druggable CRISPR-Cas method screen and multiple preclinical models, the authors found that IDH1 knockdown or pharmacologic inhibition enhanced gemcitabine efficacy. The FDA-approved allosteric IDH1 inhibitor ivosidenib showed synergistic antitumor activity with gemcitabine in wild-type IDH1 models by increasing oxidative stress, suggesting a rationale for combination therapy.

Additional publications linked IDH1 to hematologic malignancy and diagnostic pathology. In acute myeloid leukemia treated with venetoclax plus hypomethylating agents, IDH1/2 mutations were associated with favorable overall survival in a genetics-based prognostic model. In neuropathology, an immunohistochemical panel including SOX10, Olig2, and IDH1 helped distinguish oligodendrogliomas from low-grade glioneuronal tumors and assess peritumoral tumor residue, particularly in IDH1-immunonegative cases. Together, these studies portray IDH1 as a multifunctional target with roles in tumor biology, imaging, metabolic regulation, and treatment response.

Key Publications

NEWJul SOX10 distinguishes oligodendrogliomas from low-grade glioneuronal tumors/low-grade gliomas with oligodendrocyte-like features. (The journal of pathology. Clinical research, 2026, PMID 42381604): "Additionally, an immunohistochemical panel comprising SOX10, Olig2, and IDH1 aided in discriminating non-neoplastic oligodendrocyte hyperplasia from oligodendroglioma and evaluating the presence of peritumoral tumor residue, particularly in IDH1-immunonegative oligodendroglioma."
NEWJul Integrating immunohistochemical biomarkers into patient-specific reaction-diffusion models of glioblastoma growth. (Physics in medicine and biology, 2026, PMID 42259355): "The pathology-informed proliferation term allowed the model to reflect differences in tumor aggressiveness associated with Ki-67 expression and IDH-1 status."
May Novel IDH1-Targeting Fluorescent Probe Enables Intraoperative Visualization and Resection of Glioblastoma. (Analytical chemistry, 2026, PMID 42089528): "In this study, we developed a novel fluorescent probe, QM-SO3H, that targets the wild-type IDH1 enzyme to enable intraoperative navigation for glioblastoma (GBM)."
Apr [Immunotherapy and Targeted Therapy for Advanced Biliary Tract Cancer]. (The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi, 2026, PMID 42026958): "Concurrent comprehensive molecular profiling has revealed substantial genomic heterogeneity and identified actionable alterations, including fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and human epidermal growth factor receptor 2 (HER2) amplification, enabling the development of precision targeted therapies for selected patient populations."
Apr Kinsenoside Targets IDH1 to Restore Microglial Immune-Metabolic Homeostasis for Alzheimer's Disease Therapy. (Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026, PMID 41980178): "Here, we identify isocitrate dehydrogenase 1 (IDH1), a key enzyme in the TCA cycle, as a critical pathogenic driver of AD in microglia."
May The allosteric IDH1 inhibitor ivosidenib overcomes chemoresistance in intrahepatic cholangiocarcinoma models expressing wild-type IDH1. (The Journal of clinical investigation, 2026, PMID 41842958): "Here, we identified isocitrate dehydrogenase 1 (IDH1) as the crucial target that confers chemoresistance of iCCA to gemcitabine using a druggable CRISPR/Cas9 library."
May Prognostic Model Combining Mutational and Cytogenetic Profiles in Acute Myeloid Leukemia Treated with Venetoclax and Hypomethylating Agents. (Blood cancer discovery, 2026, PMID 41671569): "In multivariate analysis, mutations in TP53, KRAS, JAK2, U2AF1, CBL, and cytogenetic lesions del(7q)/-7, del(17p)/-17/i(17q), del(20q), and MECOM rearrangements predicted inferior OS, whereas IDH1/2 mutations were favorable."