ArticleFrontiers in immunology2023
The catalytic inhibitor epacadostat can affect the non-enzymatic function of IDO1.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Metabolomics and metabolites in cancer diagnosis and treatment.Molecular biomedicine · 2025Pooled it
- Research progress in metabolic reprogramming and targeting metabolic pathways for clear cell renal cell carcinoma.Genes & diseases · 2026Review
- IDO1 regulating ROS rhythm reveals glycogenolysis/PPP as a cancer treatment target.Nature chemical biology · 2026Article
- Compensatory pathways in tryptophan metabolism and immune regulation following IDO inhibition.Molecular biology reports · 2026Review
- Lactate as a Master Regulator of Immune Suppression: From Metabolic Waste to Epigenetic Checkpoint in Colorectal Cancer.International journal of molecular sciences · 2026Review
- Discovery of a Dual IDO1/TDO Inhibitor That Modulates Enzymatic Activity and IDO1/SHP-2 Signaling.Journal of medicinal chemistry · 2026Article
- Mitochondrial-Epigenetic Crosstalk in Autism Spectrum Disorder: Linking Cellular Stress to Synaptic Dysfunction and Treatment Resistance.Molecular neurobiology · 2026Review
- Extracellular ATP drives tryptophan metabolism and aryl hydrocarbon receptor activation to promote cellular senescence.The Journal of biological chemistry · 2026Article
- HCellular & molecular biology letters · 2026Article
- A Narrative Review of In Vivo Studies on the Role of Reactive Oxygen Species in Ovarian Cancer.Antioxidants (Basel, Switzerland) · 2026Review
- Modulation of the Kynurenine Pathway: A New Approach for Treating Neurodegeneration.Life (Basel, Switzerland) · 2026Review
- The kynurenine pathway in RNA virus infection: immunometabolic control of antiviral defense and viral persistence.Frontiers in immunology · 2026Review
- Beyond Glucose and Lipids: The Pivotal Role of Amino Acid Reprogramming in Shaping the Tumor Microenvironment and Guiding the Development of Novel Therapeutics.International journal of medical sciences · 2026Review
- Tryptophan metabolism in tumor immune escape: mechanisms, cellular crosstalk, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Role of Tryptophan Metabolism in Cancer.Cancer innovation · 2025Review
- Multi-Omics Advances in Major Depressive Disorder for Molecular Insights, Biomarker Discovery, and Therapeutic Development.Aging and disease · 2025Review
- Integrating artificial intelligence into small molecule development for precision cancer immunomodulation therapy.npj drug discovery · 2025Review
- IDO1 inhibition enhances CLDN18.2-CAR-T cell therapy in gastrointestinal cancers by overcoming kynurenine-mediated metabolic suppression in the tumor microenvironment.Journal of translational medicine · 2025Article
- Targeting the Kynurenine Pathway: A Novel Approach in Tumor Therapy.Expert reviews in molecular medicine · 2025Review
- The Kynurenine Pathway and Indole Pathway in Tryptophan Metabolism Influence Tumor Progression.Cancer medicine · 2025Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan metabolizing enzyme chronically activated in many cancer patients and its expression and activity correlate with a poor prognosis. In fact, it acts as an immune regulator and contributes to tumor-induced immunosuppression by determining tryptophan deprivation and producing immunosuppressive metabolites named kynurenines. These findings made IDO1 an attractive target for cancer immunotherapy and small-molecule inhibitors, such as epacadostat, have been developed to block its enzymatic activity. Although epacadostat was effective in preclinical models and in early phase trials, it gave negative results in a metastatic melanoma randomized phase III study to test the benefit of adding epacadostat to the reference pembrolizumab therapy. However, the reason for the epacadostat failure in this clinical trial has never been understood. Our data suggest that a possible explanation of epacadostat ineffectiveness may rely on the ability of this drug to enhance the other IDO1 immunoregulatory mechanism, involving intracellular signaling function. These findings open up a new perspective for IDO1 inhibitors developed as new anticancer drugs, which should be carefully evaluated for their ability to block not only the catalytic but also the signaling activity of IDO1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.