4.7 Review

Recent advances of IDH1 mutant inhibitor in cancer therapy

Related references

Note: Only part of the references are listed.
Article Biochemistry & Molecular Biology

QSAR analysis of 3-pyrimidin-4-yl-oxazolidin-2-one derivatives isocitrate dehydrogenase inhibitors using Topomer CoMFA and HQSAR methods

Jian-Bo Tong et al.

Summary: A series of mIDH1 inhibitors derived from 3-pyrimidine-4-oxazolidin-2-ketone derivatives were studied by QSAR model to explore key factors inhibiting mIDH1 activity. The generated model was validated by Topomer CoMFA, HQSAR, and PLS methods, and ten new drug molecules were designed using Topomer search technology. The results of molecular docking and ADMET testing showed the effectiveness of the newly designed drug molecules, providing a theoretical basis for the design and validation of novel mIDH1 inhibitor anticancer drugs in the future.

MOLECULAR DIVERSITY (2022)

Article Hematology

Ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed AML: a phase 1 study

Eytan M. Stein et al.

Summary: Ivosidenib and enasidenib, as targeted oral inhibitors, demonstrated good safety and efficacy when combined with intensive chemotherapy in newly diagnosed mIDH1/2 AML patients, achieving end-of-induction complete remission rates of 55% and 47% respectively.

BLOOD (2021)

Article Oncology

IDH1/2mutations in acute myeloid leukemia patients and risk of coronary artery disease and cardiac dysfunction-a retrospective propensity score analysis

Badder Kattih et al.

Summary: Clonal hematopoiesis of indeterminate potential (CHIP) is associated with mutations in leukemia genes like IDH1 and IDH2, which may increase the risk of coronary artery disease in AML patients and lead to a decline in cardiac function during treatment. Mechanistically, the oncometabolite R-2HG exacerbates doxorubicin-induced cardiotoxicity. Evaluation of IDH1/2 mutation status could help identify AML patients at risk for cardiovascular complications during cytotoxic treatment.

LEUKEMIA (2021)

Review Medicine, Research & Experimental

Targeting protein arginine methyltransferase 5 in cancers: Roles, inhibitors and mechanisms

Yingqing Chen et al.

Summary: PRMT5 functions as a crucial player in various cancers and has emerged as a promising target in cancer epigenetic therapy. There are existing PRMT5 inhibitors with different molecular mechanisms, but current issues need to be addressed to facilitate the future discovery of PRMT5 targeted drugs for cancer treatment.

BIOMEDICINE & PHARMACOTHERAPY (2021)

Article Pharmacology & Pharmacy

Selectively targeting individual bromodomain: Drug discovery and molecular mechanisms

Qianqian Wang et al.

Summary: Research has shown that although bromodomain-containing proteins exhibit high structural similarity, individual bromodomains have distinct functions and can lead to different cellular phenotypes after pharmacological inhibition. Significant progress has been made in developing bromodomain-selective inhibitors targeting BET and non-BET proteins, enriching the knowledge base for bromodomain-selective drug discovery.

PHARMACOLOGICAL RESEARCH (2021)

Article Biochemistry & Molecular Biology

Early Noninvasive Metabolic Biomarkers of Mutant IDH Inhibition in Glioma

Marina Radoul et al.

Summary: This study used H-1-MRS to identify early metabolic biomarkers of response to mutant IDH inhibition, showing significant increase in GLX and glutamate, as well as transient elevation of NAA after treatment with AG-881 and BAY-1436032. Improved animal survival and metabolic changes were observed prior to detectable differences in tumor volume between control and treated groups.

METABOLITES (2021)

Article Biochemistry & Molecular Biology

Identification and characterization of a novel mutant isocitrate dehydrogenase 1 inhibitor for glioma treatment

Na Zhang et al.

Summary: A novel mutant IDH1 inhibitor, WM17, was identified in this study, reversing the accumulation of D2HG and histone hypermethylation in IDH1 mutated cells, and significantly inhibiting cell migration.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2021)

Article Hematology

Prognostic significance of concurrent gene mutations i n intensively treated patients with IDH-mutated AML: an ALFA study

Matthieu Duchmann et al.

Summary: This study analyzed the prognostic impact of co-occurring genetic alterations and HSCT in AML patients with IDH mutations treated with IC. NPM1 mutations were found to be associated with improved overall survival in different IDH subgroups. HSCT was shown to have a positive impact on the outcomes of nonfavorable IDH1/2-mutated AML patients.

BLOOD (2021)

Article Chemistry, Medicinal

Discovery and Optimization of 2H-1λ2-Pyridin-2-one Inhibitors of Mutant Isocitrate Dehydrogenase 1 for the Treatment of Cancer

Jason M. Rohde et al.

Summary: The research focused on neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) and led to the discovery of a series of potent mIDH1 inhibitors, including the atropisomer (+)-119, which showed higher tumoral concentrations and lower 2-HG concentrations in an engineered mouse model compared to the approved drug AG-120.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Biology

Roles of metal ions in the selective inhibition of oncogenic variants of isocitrate dehydrogenase 1

Shuang Liu et al.

Summary: Liu et al investigate the effects of divalent metal ions on catalysis and inhibition of the enzyme isocitrate dehydrogenase (IDH) and its cancer-linked variant R132H. They further identify the substrates for IDH as complexes with Mg2+ and show that allosteric inhibitors work by weakening Mg2+ binding of R132H, providing mechanistic insights into the basis for selective R132H IDH1 inhibition.

COMMUNICATIONS BIOLOGY (2021)

Review Oncology

Towards precision medicine for AML

Hartmut Dohner et al.

Summary: The rapid advances in sequencing technologies have greatly improved our understanding of AML at the molecular level, leading to the development of precision medicine approaches. Challenges in this field include safely combining agents with different mechanisms of action, overcoming primary and secondary resistance, and designing future clinical trials to address these issues.

NATURE REVIEWS CLINICAL ONCOLOGY (2021)

Review Oncology

IDH Inhibitors in AML-Promise and Pitfalls

Hannah McMurry et al.

Summary: Mutations in IDH1 and IDH2 are common in AML, with inhibitors of these mutated genes now approved by the FDA for AML treatment. While IDH inhibitors show efficacy as monotherapy, they demonstrate higher response rates when combined with HMAs. Current and future trials are exploring various combination approaches, such as with standard chemotherapy, maintenance therapy, and venetoclax-based regimens, to optimize outcomes for AML patients with IDH mutations.

CURRENT HEMATOLOGIC MALIGNANCY REPORTS (2021)

Article Hematology

Additional mutations in IDH1/2-mutated patients with acute myeloid leukemia

Jingtao Lu et al.

Summary: Somatic mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) frequently occur in acute myeloid leukemia (AML) patients, showing a complex coexistence with other mutated genes, particularly those involved in transcription regulation and DNA methylation. Different IDH mutations, such as IDH2 (R140Q) and IDH2 (R172K), exhibit distinct clinical features, including age-related platelet and white blood cell count abnormalities. Further research is needed to investigate the association between IDH mutations and other genetic abnormalities that may impact disease progression and prognosis.

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY (2021)

Article Oncology

Final Overall Survival Efficacy Results of Ivosidenib for Patients With Advanced Cholangiocarcinoma With IDH1 Mutation The Phase 3 Randomized Clinical ClarIDHy Trial

Andrew X. Zhu et al.

Summary: The study found that ivosidenib was well tolerated and led to a favorable overall survival benefit compared to placebo, despite a high crossover rate.

JAMA ONCOLOGY (2021)

Article Chemistry, Medicinal

Licochalcone A suppresses the proliferation of sarcoma HT-1080 cells, as a selective R132C mutant IDH1 inhibitor

Chujiao Hu et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2020)

Article Biochemistry & Molecular Biology

The Tricarboxylic Acid Cycle at the Crossroad Between Cancer and Immunity

Alessandra Scagliola et al.

ANTIOXIDANTS & REDOX SIGNALING (2020)

Article Chemistry, Medicinal

Structure-Based Design and Identification of FT-2102 (Olutasidenib), a Potent Mutant-Selective IDH1 Inhibitor

Justin A. Caravella et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

Article Chemistry, Medicinal

Vorasidenib (AG-881): A First-in-Class, Brain-Penetrant Dual Inhibitor of Mutant IDH1 and 2 for Treatment of Glioma

Zenon Konteatis et al.

ACS MEDICINAL CHEMISTRY LETTERS (2020)

Review Oncology

IDH mutation in glioma: molecular mechanisms and potential therapeutic targets

Sue Han et al.

BRITISH JOURNAL OF CANCER (2020)

Review Oncology

Immunotherapy for glioma: Current management and future application

Shengchao Xu et al.

CANCER LETTERS (2020)

Article Pharmacology & Pharmacy

Discovery of Novel IDH1 Inhibitor Through Comparative Structure-Based Virtual Screening

Yuwei Wang et al.

FRONTIERS IN PHARMACOLOGY (2020)

Review Oncology

The Time Has Come for Targeted Therapies for AML: Lights and Shadows

Alessandro Fiorentini et al.

ONCOLOGY AND THERAPY (2020)

Article Biochemistry & Molecular Biology

Discovery of DC_H31 as potential mutant IDH1 inhibitor through NADPH-based high throughput screening

Zhe Duan et al.

BIOORGANIC & MEDICINAL CHEMISTRY (2019)

Review Oncology

Mutant Isocitrate Dehydrogenase Inhibitors as Targeted Cancer Therapeutics

Danielle Golub et al.

FRONTIERS IN ONCOLOGY (2019)

Article Pharmacology & Pharmacy

I-8, a novel inhibitor of mutant IDH1, inhibits cancer progression in vitro and in vivo

Panli Jia et al.

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES (2019)

Article Biochemistry & Molecular Biology

Synthesis and biological evaluation of 3-aryl-4-indolyl-maleimides as potent mutant isocitrate dehydrogenase-1 inhibitors

Xiaoqi Liu et al.

BIOORGANIC & MEDICINAL CHEMISTRY (2019)

Article Chemistry, Medicinal

Discovery of new small molecule inhibitors targeting isocitrate dehydrogenase 1 (IDH1) with blood-brain barrier penetration

Hengyi Cao et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2019)

Article Chemistry, Medicinal

Identification of novel allosteric inhibitors of mutant isocitrate dehydrogenase 1 by cross docking-based virtual screening

Fangxia Zou et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2018)

Article Biochemistry & Molecular Biology

Steroids from Ganoderma sinense as new natural inhibitors of cancer-associated mutant IDH1

Mengzhu Zheng et al.

BIOORGANIC CHEMISTRY (2018)

Article Biochemistry & Molecular Biology

IDH1 Arg-132 mutant promotes tumor formation through down-regulating p53

Bin Jiang et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2018)

Article Chemistry, Medicinal

Inhibition of Mutated Isocitrate Dehydrogenase 1 in Cancer

Fangrui Wu et al.

MEDICINAL CHEMISTRY (2018)

Article Chemistry, Medicinal

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

Janeta Popovici-Muller et al.

ACS MEDICINAL CHEMISTRY LETTERS (2018)

Article Biochemistry & Molecular Biology

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

Rui Ma et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2018)

Review Clinical Neurology

Glioma Subclassifications and Their Clinical Significance

Ricky Chen et al.

NEUROTHERAPEUTICS (2017)

Article Chemistry, Medicinal

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

Julian R. Levell et al.

ACS MEDICINAL CHEMISTRY LETTERS (2017)

Article Chemistry, Medicinal

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

Young Shin Cho et al.

ACS MEDICINAL CHEMISTRY LETTERS (2017)

Article Biochemistry & Molecular Biology

Breaking Cryo-EM Resolution Barriers to Facilitate Drug Discovery

Alan Merk et al.

Article Chemistry, Medicinal

Discovery of 8-Membered Ring Sulfonamides as Inhibitors of Oncogenic Mutant Isocitrate Dehydrogenase 1

Jason M. Law et al.

ACS MEDICINAL CHEMISTRY LETTERS (2016)

Article Chemistry, Medicinal

Inhibition of Cancer-Associated Mutant Isocitrate Dehydrogenases by 2-Thiohydantoin Compounds

Fangrui Wu et al.

JOURNAL OF MEDICINAL CHEMISTRY (2015)

Article Biochemistry & Molecular Biology

New IDH1 mutant inhibitors for treatment of acute myeloid leukemia

Ujunwa C. Okoye-Okafor et al.

NATURE CHEMICAL BIOLOGY (2015)

Article Medicine, General & Internal

Glioma

Michael Weller et al.

NATURE REVIEWS DISEASE PRIMERS (2015)

Article Neurosciences

Effective immuno-targeting of the IDH1 mutation R132H in a murine model of intracranial glioma

Serena Pellegatta et al.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2015)

Article Biochemistry & Molecular Biology

Biochemical, Cellular, and Biophysical Characterization of a Potent Inhibitor of Mutant Isocitrate Dehydrogenase IDH1

Mindy I. Davis et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2014)

Article Multidisciplinary Sciences

A vaccine targeting mutant IDH1 induces antitumour immunity

Theresa Schumacher et al.

NATURE (2014)

Editorial Material Oncology

Releasing the Block: Setting Differentiation Free with Mutant IDH Inhibitors

Christopher J. Pirozzi et al.

CANCER CELL (2013)

Review Chemistry, Multidisciplinary

Drug repositioning by structure-based virtual screening

Dik-Lung Ma et al.

CHEMICAL SOCIETY REVIEWS (2013)

Review Cell Biology

What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer

Julie-Aurore Losman et al.

GENES & DEVELOPMENT (2013)

Article Chemistry, Medicinal

Crystallographic Investigation and Selective Inhibition of Mutant Isocitrate Dehydrogenase

Baisong Zheng et al.

ACS MEDICINAL CHEMISTRY LETTERS (2013)

Article Multidisciplinary Sciences

Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation

Peppi Koivunen et al.

NATURE (2012)

Article Biochemistry & Molecular Biology

Enzyme redesign guided by cancer-derived IDH1 mutations

Zachary J. Reitman et al.

NATURE CHEMICAL BIOLOGY (2012)

Article Chemistry, Medicinal

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

Janeta Popovici-Muller et al.

ACS MEDICINAL CHEMISTRY LETTERS (2012)

Article Biochemistry & Molecular Biology

The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases

Rasheduzzaman Chowdhury et al.

EMBO REPORTS (2011)

Article Pharmacology & Pharmacy

THE VALUE OF DRUG REPOSITIONING IN THE CURRENT PHARMACEUTICAL MARKET

Edward L. Tobinick

DRUG NEWS & PERSPECTIVES (2009)

Article Multidisciplinary Sciences

An integrated genomic analysis of human glioblastoma Multiforme

D. Williams Parsons et al.

SCIENCE (2008)

Article Multidisciplinary Sciences

The consensus coding sequences of human breast and colorectal cancers

Tobias Sjoeblom et al.

SCIENCE (2006)

Article Biochemistry & Molecular Biology

Substrate-free structure of a monomeric NADP isocitrate dehydrogenase: An open conformation phylogenetic relationship of isocitrate dehydrogenase

F Imabayashi et al.

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS (2006)

Correction Medicine, General & Internal

Clomiphene citrate for ovulation induction in women with oligo-amenorrhoea (Withdrawn Paper. 1996, art. no. CD000056.pub2)

E Hughes et al.

COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2005)

Correction Medicine, General & Internal

Clomiphene citrate for ovulation induction in women with oligo-amenorrhoea (Withdrawn paper. 1996, art. no. CD000056)

E Hughes et al.

COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2005)

Correction Medicine, General & Internal

Clomiphene citrate for ovulation induction in women with oligo-amenorrhoea (Withdrawn Paper. 1996, art. no. CD000056.pub2)

E Hughes et al.

COCHRANE DATABASE OF SYSTEMATIC REVIEWS (2005)