Mutant Isocitrate Dehydrogenase Inhibitors as Targeted Cancer Therapeutics

IDH3α regulates one-carbon metabolism in glioblastoma

(2019) Jasmine L. May et al.   Science Advances

Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet

(2019) Miguel A. Sanz et al.   BLOOD

Enasidenib, a targeted inhibitor of mutant IDH2 proteins for treatment of relapsed or refractory acute myeloid leukemia

(2018) Eytan M Stein   Future Oncology

Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML

(2018) Courtney D. DiNardo et al.   NEW ENGLAND JOURNAL OF MEDICINE

Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers

(2018) Janeta Popovici-Muller et al.   ACS Medicinal Chemistry Letters

Differentiation Syndrome Associated With Enasidenib, a Selective Inhibitor of Mutant Isocitrate Dehydrogenase 2

(2018) Amir T. Fathi et al.   JAMA Oncology

Beyond Brooding on Oncometabolic Havoc in IDH-Mutant Gliomas and AML: Current and Future Therapeutic Strategies

(2018) Hanumantha Madala et al.   Cancers

Crystal structures of pan-IDH inhibitor AG-881 in complex with mutant human IDH1 and IDH2

(2018) Rui Ma et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Abstract 4956: Functional characterization of the ivosidenib (AG-120) and azacitidine combination in a mutant IDH1 AML cell model

(2018) Katharine Yen et al.   CANCER RESEARCH

Isocitrate dehydrogenase 1 mutation sensitizes intrahepatic cholangiocarcinoma to the BET inhibitor JQ1

(2018) Hiroaki Fujiwara et al.   CANCER SCIENCE

Ivosidenib: First Global Approval

(2018) Sohita Dhillon   DRUGS

Pharmacokinetics/pharmacodynamics (PK/PD) of ivosidenib in patients with IDH1-mutant advanced solid tumors from a phase 1 study.

(2018) Bin Fan et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase 1 study of AG-881, an inhibitor of mutant IDH1/IDH2, in patients with advanced IDH-mutant solid tumors, including glioma.

(2018) Ingo K. Mellinghoff et al.   JOURNAL OF CLINICAL ONCOLOGY

A phase 1 dose escalation study of the IDH1m inhibitor, FT-2102, in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

(2018) Justin M. Watts et al.   JOURNAL OF CLINICAL ONCOLOGY

Mutant IDH (mIDH) inhibitors, ivosidenib or enasidenib, with azacitidine (AZA) in patients with acute myeloid leukemia (AML).

(2018) Courtney Denton Dinardo et al.   JOURNAL OF CLINICAL ONCOLOGY

AGILE: A phase 3, multicenter, randomized, placebo-controlled study of ivosidenib in combination with azacitidine in adult patients with previously untreated acute myeloid leukemia with an IDH1 mutation.

(2018) Eytan Stein et al.   JOURNAL OF CLINICAL ONCOLOGY

Acquired resistance to IDH inhibition through trans or cis dimer-interface mutations

(2018) Andrew M. Intlekofer et al.   NATURE

Demethylation and epigenetic modification with 5-azacytidine reduces IDH1 mutant glioma growth in combination with temozolomide

(2018) Alex Shimura Yamashita et al.   NEURO-ONCOLOGY

SOHO State of the Art Update and Next Questions: IDH Therapeutic Targeting in AML

(2018) Courtney D. DiNardo et al.   Clinical Lymphoma Myeloma & Leukemia

Epigenetic Modifiers in Myeloid Malignancies: The Role of Histone Deacetylase Inhibitors

(2018) Johanna Ungerstedt   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ACTR-31. PHASE 1 STUDY OF AG-881, AN INHIBITOR OF MUTANT IDH1 AND IDH2: RESULTS FROM THE RECURRENT/PROGRESSIVE GLIOMA POPULATION

(2018) Ingo Mellinghoff et al.   NEURO-ONCOLOGY

RBTT-03. A PHASE 1, MULTICENTER, RANDOMIZED, OPEN-LABEL, PERIOPERATIVE STUDY OF AG-120 (IVOSIDENIB) AND AG-881 IN PATIENTS WITH RECURRENT, NONENHANCING, IDH1-MUTANT, LOW-GRADE GLIOMA

(2018) Ingo Mellinghoff et al.   NEURO-ONCOLOGY

Isoform Switching as a Mechanism of Acquired Resistance to Mutant Isocitrate Dehydrogenase Inhibition

(2018) James J. Harding et al.   Cancer Discovery

Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo

(2017) A Chaturvedi et al.   LEUKEMIA

Leukemic Transformation in Myeloproliferative Neoplasms

(2017) Meera Yogarajah et al.   MAYO CLINIC PROCEEDINGS

Mutant IDH1 Disrupts the Mouse Subventricular Zone and Alters Brain Tumor Progression

(2017) Christopher J. Pirozzi et al.   MOLECULAR CANCER RESEARCH

Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence

(2017) Sevin Turcan et al.   NATURE GENETICS

Glioma CpG island methylator phenotype (G-CIMP): biological and clinical implications

(2017) Tathiane M Malta et al.   NEURO-ONCOLOGY

EXTH-59. THE IDH1 MUTANT INHIBITOR AG-120 SHOWS STRONG INHIBITION OF 2-HG PRODUCTION IN AN ORTHOTOPIC IDH1 MUTANT GLIOMA MODEL IN VIVO

(2017) Brandon Nicolay et al.   NEURO-ONCOLOGY

Optimization of 3-Pyrimidin-4-yl-oxazolidin-2-ones as Allosteric and Mutant Specific Inhibitors of IDH1

(2017) Julian R. Levell et al.   ACS Medicinal Chemistry Letters

Discovery and Evaluation of Clinical Candidate IDH305, a Brain Penetrant Mutant IDH1 Inhibitor

(2017) Young Shin Cho et al.   ACS Medicinal Chemistry Letters

Optimizing Next-Generation AML Therapy: Activity of Mutant IDH2 Inhibitor AG-221 in Preclinical Models

(2017) Daniel Thomas et al.   Cancer Discovery

AG-221, a First-in-Class Therapy Targeting Acute Myeloid Leukemia Harboring Oncogenic IDH2 Mutations

(2017) Katharine Yen et al.   Cancer Discovery

HMGB1 promotes differentiation syndrome by inducing hyperinflammation via MEK/ERK signaling in acute promyelocytic leukemia cells

(2017) Lanlan Tang et al.   Oncotarget

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

(2017) Farshad Farshidfar et al.   Cell Reports

Cancer-Associated IDH1 Promotes Growth and Resistance to Targeted Therapies in the Absence of Mutation

(2017) Andrea E. Calvert et al.   Cell Reports

Low-Grade Astrocytoma Mutations in IDH1, P53, and ATRX Cooperate to Block Differentiation of Human Neural Stem Cells via Repression of SOX2

(2017) Aram S. Modrek et al.   Cell Reports

m 6 A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells

(2017) Qi Cui et al.   Cell Reports

Therapeutic Targeting of Histone Modifications in Adult and Pediatric High-Grade Glioma

(2017) Maria J. Williams et al.   Frontiers in Oncology

Pharmacologic Targeting of Chromatin Modulators As Therapeutics of Acute Myeloid Leukemia

(2017) Rui Lu et al.   Frontiers in Oncology

Allosteric inhibitor remotely modulates the conformation of the orthestric pockets in mutant IDH2/R140Q

(2017) Jiao Chen et al.   Scientific Reports

A Brain Penetrant Mutant IDH1 Inhibitor Provides In Vivo Survival Benefit

(2017) Johnny Kopinja et al.   Scientific Reports

Interrogating the Druggability of the 2-Oxoglutarate-Dependent Dioxygenase Target Class by Chemical Proteomics

(2016) Gérard Joberty et al.   ACS Chemical Biology

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel

(2016) Hartmut Döhner et al.   BLOOD

Mutant IDH1 Downregulates ATM and Alters DNA Repair and Sensitivity to DNA Damage Independent of TET2

(2016) Satoshi Inoue et al.   CANCER CELL

Expression of Idh1R132H in the Murine Subventricular Zone Stem Cell Niche Recapitulates Features of Early Gliomagenesis

(2016) Chiara Bardella et al.   CANCER CELL

Molecular Pathways: Isocitrate Dehydrogenase Mutations in Cancer

(2016) O. Clark et al.   CLINICAL CANCER RESEARCH

Evidence for Clinical Differentiation and Differentiation Syndrome in Patients With Acute Myeloid Leukemia and IDH1 Mutations Treated With the Targeted Mutant IDH1 Inhibitor, AG-120

(2016) K.C. Birendra et al.   Clinical Lymphoma Myeloma & Leukemia

A Concise Update on Risk Factors, Therapy, and Outcome of Leukemic Transformation of Myeloproliferative Neoplasms

(2016) John Mascarenhas   Clinical Lymphoma Myeloma & Leukemia

Isocitrate dehydrogenase mutations in myeloid malignancies

(2016) B C Medeiros et al.   LEUKEMIA

The Evolving Landscape in the Development of Isocitrate Dehydrogenase Mutant Inhibitors

(2016) Jiao Chen et al.   MINI-REVIEWS IN MEDICINAL CHEMISTRY

Rapid Conversion of Mutant IDH1 from Driver to Passenger in a Model of Human Gliomagenesis

(2016) T.-C. A. Johannessen et al.   MOLECULAR CANCER RESEARCH

Mutations of myelodysplastic syndromes (MDS): An update

(2016) Bani Bandana Ganguly et al.   MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH

ACTR-46. AG120, A FIRST-IN-CLASS MUTANT IDH1 INHIBITOR IN PATIENTS WITH RECURRENT OR PROGRESSIVE IDH1 MUTANT GLIOMA: RESULTS FROM THE PHASE 1 GLIOMA EXPANSION COHORTS

(2016) Ingo K. Mellinghoff et al.   NEURO-ONCOLOGY

Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML

(2015) Courtney D. DiNardo et al.   AMERICAN JOURNAL OF HEMATOLOGY

Presence of isocitrate dehydrogenase mutations may predict clinical response to hypomethylating agents in patients with acute myeloid leukemia

(2015) Ashkan Emadi et al.   AMERICAN JOURNAL OF HEMATOLOGY

Extreme Vulnerability of IDH1 Mutant Cancers to NAD+ Depletion

(2015) Kensuke Tateishi et al.   CANCER CELL

Molecular Pathogenesis and Targeted Therapies for Intrahepatic Cholangiocarcinoma

(2015) A. Moeini et al.   CLINICAL CANCER RESEARCH

Abstract PL04-05: The first reported results of AG-120, a first-in-class, potent inhibitor of the IDH1 mutant protein, in a Phase I study of patients with advanced IDH1-mutant solid tumors, including gliomas

(2015) Howard Burris et al.   MOLECULAR CANCER THERAPEUTICS

Insulator dysfunction and oncogene activation in IDH mutant gliomas

(2015) William A. Flavahan et al.   NATURE

New IDH1 mutant inhibitors for treatment of acute myeloid leukemia

(2015) Ujunwa C Okoye-Okafor et al.   Nature Chemical Biology

Acute Myeloid Leukemia

(2015) Hartmut Döhner et al.   NEW ENGLAND JOURNAL OF MEDICINE

Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas

(2015)   NEW ENGLAND JOURNAL OF MEDICINE

Treatment with a Small Molecule Mutant IDH1 Inhibitor Suppresses Tumorigenic Activity and Decreases Production of the Oncometabolite 2-Hydroxyglutarate in Human Chondrosarcoma Cells

(2015) Luyuan Li et al.   PLoS One

Epigenetic therapy of cancer stem and progenitor cells by targeting DNA methylation machineries

(2015) Patompon Wongtrakoongate   World Journal of Stem Cells

5-azacytidine reduces methylation, promotes differentiation and induces tumor regression in a patient-derived IDH1 mutant glioma xenograft

(2015) Alexandra Borodovsky et al.   Oncotarget

Efficient induction of differentiation and growth inhibition in IDH1 mutant glioma cells by the DNMT Inhibitor Decitabine.

(2015) Sevin Turcan et al.   Oncotarget

IDH2 mutation-induced histone and DNA hypermethylation is progressively reversed by small-molecule inhibition

(2014) A. Kernytsky et al.   BLOOD

Selective Inhibition of Mutant Isocitrate Dehydrogenase 1 (IDH1) via Disruption of a Metal Binding Network by an Allosteric Small Molecule

(2014) Gejing Deng et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies

(2014) A P Im et al.   LEUKEMIA

IDH2mutation in gliomas including novel mutation

(2014) Jaemoon Koh et al.   NEUROPATHOLOGY

Mutant IDH1 promotes leukemogenesis in vivo and can be specifically targeted in human AML

(2013) A. Chaturvedi et al.   BLOOD

Serum 2-hydroxyglutarate levels predict isocitrate dehydrogenase mutations and clinical outcome in acute myeloid leukemia

(2013) C. D. DiNardo et al.   BLOOD

Predictive factors for all-trans retinoic acid-related differentiation syndrome in patients with acute promyelocytic leukemia

(2013) Houry Leblebjian et al.   LEUKEMIA RESEARCH

Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China

(2013) J.-H. Wang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Mutational Analysis Reveals the Origin and Therapy-Driven Evolution of Recurrent Glioma

(2013) B. E. Johnson et al.   SCIENCE

An Inhibitor of Mutant IDH1 Delays Growth and Promotes Differentiation of Glioma Cells

(2013) D. Rohle et al.   SCIENCE

Targeted Inhibition of Mutant IDH2 in Leukemia Cells Induces Cellular Differentiation

(2013) F. Wang et al.   SCIENCE

DNA methyltransferase 1 is essential for initiation of the colon cancers

(2012) Rena Morita et al.   EXPERIMENTAL AND MOLECULAR PATHOLOGY

Emerging insights into the molecular and cellular basis of glioblastoma

(2012) G. P. Dunn et al.   GENES & DEVELOPMENT

The Potential for Isocitrate Dehydrogenase Mutations to Produce 2-Hydroxyglutarate Depends on Allele Specificity and Subcellular Compartmentalization

(2012) Patrick S. Ward et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype

(2012) Sevin Turcan et al.   NATURE

Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid Leukemia

(2012) Jay P. Patel et al.   NEW ENGLAND JOURNAL OF MEDICINE

Discovery of the First Potent Inhibitors of Mutant IDH1 That Lower Tumor 2-HG in Vivo

(2012) Janeta Popovici-Muller et al.   ACS Medicinal Chemistry Letters

Prognostic implications of the IDH1 synonymous SNP rs11554137 in pediatric and adult AML: a report from the Children's Oncology Group and SWOG

(2011) P. A. Ho et al.   BLOOD

The prognostic significance of IDH2 mutations in AML depends on the location of the mutation

(2011) C. L. Green et al.   BLOOD

Oncometabolite 2-Hydroxyglutarate Is a Competitive Inhibitor of α-Ketoglutarate-Dependent Dioxygenases

(2011) Wei Xu et al.   CANCER CELL

The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases

(2011) Rasheduzzaman Chowdhury et al.   EMBO REPORTS

IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours

(2011) M Fernanda Amary et al.   JOURNAL OF PATHOLOGY

Screen for IDH1, IDH2, IDH3, D2HGDH and L2HGDH Mutations in Glioblastoma

(2011) Daniel Krell et al.   PLoS One

THE DIFFERENTIATION SYNDROME IN PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA: EXPERIENCE OF THE PETHEMA GROUP AND REVIEW OF THE LITERATURE.

(2011) Pau Montesinos et al.   Mediterranean Journal of Hematology and Infectious Diseases

The prognostic IDH1 R132 mutation is associated with reduced NADP+-dependent IDH activity in glioblastoma

(2010) Fonnet E. Bleeker et al.   ACTA NEUROPATHOLOGICA

The prognostic significance of IDH1 mutations in younger adult patients with acute myeloid leukemia is dependent on FLT3/ITD status

(2010) C. L. Green et al.   BLOOD

Prognostic impact of IDH2 mutations in cytogenetically normal acute myeloid leukemia

(2010) F. Thol et al.   BLOOD

Advances in understanding the pulmonary infiltration in acute promyelocytic leukaemia

(2010) Maaike Luesink et al.   BRITISH JOURNAL OF HAEMATOLOGY

The Common Feature of Leukemia-Associated IDH1 and IDH2 Mutations Is a Neomorphic Enzyme Activity Converting α-Ketoglutarate to 2-Hydroxyglutarate

(2010) Patrick S. Ward et al.   CANCER CELL

Molecular mechanisms of “off-on switch” of activities of human IDH1 by tumor-associated mutation R132H

(2010) Bei Yang et al.   CELL RESEARCH

Impact of IDH1 R132 Mutations and an IDH1 Single Nucleotide Polymorphism in Cytogenetically Normal Acute Myeloid Leukemia: SNP rs11554137 Is an Adverse Prognostic Factor

(2010) Katharina Wagner et al.   JOURNAL OF CLINICAL ONCOLOGY

IDH1andIDH2Gene Mutations Identify Novel Molecular Subsets Within De Novo Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study

(2010) Guido Marcucci et al.   JOURNAL OF CLINICAL ONCOLOGY

Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas

(2009) Christian Hartmann et al.   ACTA NEUROPATHOLOGICA

IDH1 Mutations Are Early Events in the Development of Astrocytomas and Oligodendrogliomas

(2009) Takuya Watanabe et al.   AMERICAN JOURNAL OF PATHOLOGY

Mutant Metabolic Enzymes Are at the Origin of Gliomas

(2009) H. Yan et al.   CANCER RESEARCH

IDH1mutations at residue p.R132 (IDH1R132) occur frequently in high-grade gliomas but not in other solid tumors

(2009) Fonnet E. Bleeker et al.   HUMAN MUTATION

High body mass index is an independent predictor of differentiation syndrome in patients with acute promyelocytic leukemia

(2009) Ramzi Jeddi et al.   LEUKEMIA RESEARCH

Cancer-associated IDH1 mutations produce 2-hydroxyglutarate

(2009) Lenny Dang et al.   NATURE

Recurring Mutations Found by Sequencing an Acute Myeloid Leukemia Genome

(2009) Elaine R. Mardis et al.   NEW ENGLAND JOURNAL OF MEDICINE

IDH1andIDH2Mutations in Gliomas

(2009) Hai Yan et al.   NEW ENGLAND JOURNAL OF MEDICINE

Arsenic trioxide: safety issues and their management

(2008) Wing-Yan AU et al.   ACTA PHARMACOLOGICA SINICA

Differentiation syndrome in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline chemotherapy: characteristics, outcome, and prognostic factors

(2008) P. Montesinos et al.   BLOOD

An Integrated Genomic Analysis of Human Glioblastoma Multiforme

(2008) D. W. Parsons et al.   SCIENCE