Cited by 478Acute Myeloid Leukemia ResearchGlioma Diagnosis and TreatmentChromatin Remodeling and Cancer

The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.

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

Yen, Katharine, Travins, Jeremy, Wang, Fang, David, Muriel D., Artin, Erin, Straley, Kimberly, Padyana, Anil, Gross, Stefan, DeLaBarre, Byron, Tobin, Erica, Chen, Yue, Nagaraja, Raj, Choe, Sung, Jin, Lei, Konteatis, Zenon, Cianchetta, Giovanni, Saunders, Jeffrey O., Salituro, Francesco G., Quivoron, Cyril, Opolon, Paule, Bawa, Olivia, Saada, Véronique, Paci, Angelo, Broutin, Sophie, Bernard, Olivier A., de Botton, Stéphane, Marteyn, Benoît S., Pilichowska, Monika, Xu, YingXia, Fang, Cheng, Jiang, Fan, Wei, Wentao, Jin, Shengfang, Silverman, Lee, Liu, Wei, Yang, Hua, Dang, Lenny, Dorsch, Marion, Penard-Lacronique, Virginie, Biller, Scott A., Su, Shin-San Michael·2017·Cancer Discovery

DOI 10.1158/2159-8290.cd-16-1034

Published version of a preprint

Open this paper in CoChat — free account

Abstract

Somatic gain-of-function mutations in isocitrate dehydrogenases (IDH) 1 and 2 are found in multiple hematologic and solid tumors, leading to accumulation of the oncometabolite (R)-2-hydroxyglutarate (2HG). 2HG competitively inhibits α-ketoglutarate–dependent dioxygenases, including histone demethylases and methylcytosine dioxygenases of the TET family, causing epigenetic dysregulation and a block in cellular differentiation. In vitro studies have provided proof of concept for mutant IDH inhibition as a therapeutic approach. We report the discovery and characterization of AG-221, an orally available, selective, potent inhibitor of the mutant IDH2 enzyme. AG-221 suppressed 2HG production and induced cellular differentiation in primary human IDH2 mutation–positive acute myeloid leukemia (AML) cells ex vivo and in xenograft mouse models. AG-221 also provided a statistically significant survival benefit in an aggressive IDH2R140Q-mutant AML xenograft mouse model. These findings supported initiation of the ongoing clinical trials of AG-221 in patients with IDH2 mutation–positive advanced hematologic malignancies. Significance: Mutations in IDH1/2 are identified in approximately 20% of patients with AML and contribute to leukemia via a block in hematopoietic cell differentiation. We have shown that the targeted inhibitor AG-221 suppresses the mutant IDH2 enzyme in multiple preclinical models and induces differentiation of malignant blasts, supporting its clinical development. Cancer Discov; 7(5); 478–93. ©2017 AACR. See related commentary by Thomas and Majeti, p. 459. See related article by Shih et al., p. 494. This article is highlighted in the In This Issue feature, p. 443

Integrity signals

Registry

Crossref · 10.1158/2159-8290.cd-16-1034

Cites

52 of 52 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 29,915
Phaser crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612
NMRPipe: A multidimensional spectral processing system based on UNIX pipes
Delaglio, F., Grzesiek, S., Vuister, G. W., Zhu, G., Pfeifer, J., & Bax, A. (1995) · Journal of Biomolecular NMR · doi:10.1007/bf00197809 · Cited by 15,961
REFMAC 5 for the refinement of macromolecular crystal structures
Murshudov, G. N., Skubák, P., Lebedev, A. A., Pannu, N. S., Steiner, R. A., Nicholls, R. A., Winn, M., Long, F., & Vagin, A. A. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444911001314 · Cited by 8,415
The emerging hallmarks of cancer metabolism
Pavlova, N. N., & Thompson, C. B. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.006 · Cited by 5,926 · cited 1×
“Metabolic reprogramming is a hallmark of cancer, contributing to the initiation and maintenance of tumors (1, 2).”
Background
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
Parsons, D. W., Jones, S., Zhang, X., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.-M., Gallia, G. L., et al. (2008) · Science · doi:10.1126/science.1164382 · Cited by 5,857
IDH1 and IDH2 Mutations in Gliomas
Yan, H., Parsons, D. W., Jin, G., McLendon, R., Rasheed, B. A., Yuan, W., Kos, I., Batinic-Haberle, I., Jones, S., Riggins, G. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808710 · Cited by 5,847
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2009) · Nature · doi:10.1038/nature08617 · Cited by 4,154
Self-citation

Show all 52 references

Sorted by citations

Items 201–300 of 478

Epigenetic Regulators of DNA Cytosine Modification: Promising Targets for Cancer Therapy
Jung, I., An, J., & Ko, M. (2023) · Biomedicines · doi:10.3390/biomedicines11030654 · Cited by 22
Enasidenib in the treatment of relapsed/refractory acute myeloid leukemia: an evidence-based review of its place in therapy
Galkin, M., & Jonas, B. A. (2019) · Core evidence · doi:10.2147/ce.s172912 · Cited by 22
“It was also noted that enasidenib is not cytotoxic to IDH2 mutant cells; rather, it induces a differentiation effect, and mature neutrophils which develop in cells treated with enasidenib continue to carry the mutant allele.(33) Based on the successes of preclinical studies, a multicenter Phase I/II trial was initiate…”
Background
Novel Mitochondria-targeted Drugs for Cancer Therapy
Fialová, J. L., Raudenská, M., Jakubek, M., Kejík, Z., Pavel Martasek, E., Babula, P., Matkowski, A., Filipenský, P., & Masařík, M. (2020) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557520666201118153242 · Cited by 22
Promising Molecular Targets for the Targeted Therapy of Biliary Tract Cancers: An Overview
Yang, W., & Sun, Y. (2021) · OncoTargets and Therapy · doi:10.2147/ott.s297643 · Cited by 22
Assessing acquired resistance to IDH1 inhibitor therapy by full-exon IDH1 sequencing and structural modelingPreprint
Oltvai, Z. N., Harley, S. E., Koes, D. R., Michel, S. N., Warlick, E. D., Nelson, A., Yohe, S. L., & Mroz, P. (2021) · Molecular Case Studies · doi:10.1101/mcs.a006007 · Cited by 24
“Targeted inhibition of pathogenic IDH1/2 variants has been shown to reduce the production of 2-HG and decrease leukemic burden (Chaturvedi et al. 2013; Wang et al. 2013; Upadhyay et al. 2017; Yen et al. 2017).”
Background
Novel Therapies for Acute Myeloid Leukemia: Are We Finally Breaking the Deadlock?
Stahl, M. F., Lu, B. Y., Kim, T. K., & Zeidan, A. M. (2017) · Targeted Oncology · doi:10.1007/s11523-017-0503-8 · Cited by 22
“AG-221 was shown to suppress 2HG production and induce cellular differentiation in in vitro and ex vivo models [154].”
Background
The new perspectives of targeted therapy in acute myeloid leukemia
Walasek, A. (2018) · Advances in Clinical and Experimental Medicine · doi:10.17219/acem/81610 · Cited by 21
IDH1/2 Mutations in Cancer Stem Cells and Their Implications for Differentiation Therapy
Molenaar, R. J., & Wilmink, J. W. (2021) · Journal of Histochemistry & Cytochemistry · doi:10.1369/00221554211062499 · Cited by 22
RNA binding motif protein 45-mediated phosphorylation enhances protein stability of ASCT2 to promote hepatocellular carcinoma progression
Du, D., Qin, M., Shi, L., Liu, C., Jiang, J., Liao, Z., Wang, H., Zhang, Z., Sun, L., Fan, H., et al. (2023) · Oncogene · doi:10.1038/s41388-023-02795-3 · Cited by 20
“AG-221 is known as a mutant isocitrate dehydrogenase (mIDH2) inhibitor for acute myeloid leukemia therapy which harbors oncogenic IDH2 mutations [50].”
Background
Preclinical pharmacology modeling of chimeric antigen receptor T therapies
Kumari, R., Ouyang, X., Wang, J., Xu, X., Zheng, M., An, X., & Li, Q. (2021) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2021.08.008 · Cited by 21
Exploiting Electrode Nanoconfinement to Investigate the Catalytic Properties of Isocitrate Dehydrogenase (IDH1) and a Cancer-Associated Variant
Herold, R. A., Reinbold, R., Megarity, C. F., Abboud, M. I., Schofield, C. J., & Armstrong, F. A. (2021) · The Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.1c01517 · Cited by 20
Acute myeloid leukemia: Therapy resistance and a potential role for tetraspanin membrane scaffolds
Floren, M., & Gillette, J. M. (2021) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2021.106029 · Cited by 20
Glioma-Targeted Therapeutics: Computer-Aided Drug Design Prospective
Poonan, P., Agoni, C., Ibrahim, M. A. A., & Soliman, M. E. S. (2021) · The Protein Journal · doi:10.1007/s10930-021-10021-w · Cited by 20
Therapeutic implications of mitochondrial stress–induced proteasome inhibitor resistance in multiple myeloma
Sharma, A., Nair, R., Achreja, A., Mittal, A., Gupta, P., Balakrishnan, K., Edgar, C. L., Animasahun, O. H., Dwivedi, B., Barwick, B. G., et al. (2022) · Science Advances · doi:10.1126/sciadv.abq5575 · Cited by 22
“We found that IACS and enasidenib [a mutant IDH2 inhibitor (35)] synergized with each other (fig.”
Background
Isocitrate dehydrogenase 2 mutations correlate with leukemic transformation and are predicted by 2-hydroxyglutarate in myelodysplastic syndromes
Lin, P., Luo, Y., Zhu, S., Maggio, D. M., Yang, H., Hu, C., Wang, J., Zhang, H., Ren, Y., Zhou, X., et al. (2018) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-018-2627-3 · Cited by 20
Self-citation
Refining AML Treatment: The Role of Genetics in Response and Resistance Evaluation to New Agents
Halik, A., Arends, C. M., Bullinger, L., Damm, F., & Frick, M. (2022) · Cancers · doi:10.3390/cancers14071689 · Cited by 20
Targeting epigenetic regulation for cancer therapy using small molecule inhibitors
Kumar, A., Emdad, L., Fisher, P. B., & Das, S. K. (2023) · Advances in cancer research · doi:10.1016/bs.acr.2023.01.001 · Cited by 20
Identification of a selective inhibitor of IDH2/R140Q enzyme that induces cellular differentiation in leukemia cells
Chen, J., Yang, J., Wei, Q., Weng, L., Wu, F., Shi, Y. Y., Cheng, X., Cai, X., Hu, C., & Cao, P. (2020) · Cell Communication and Signaling · doi:10.1186/s12964-020-00536-7 · Cited by 19
Discovery of new small molecule inhibitors targeting isocitrate dehydrogenase 1 (IDH1) with blood-brain barrier penetration
Cao, H., Zhu, G., Sun, L., Chen, G., Ma, X., Luo, X., & Zhu, J. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.111694 · Cited by 18
Isocitrate Dehydrogenase Mutant Grade II and III Glial Neoplasms
Mellinghoff, I. K., Chang, S. M., Jaeckle, K. A., & van den Bent, M. J. (2021) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2021.08.008 · Cited by 21
Acute myeloid leukemia maturation lineage influences residual disease and relapse following differentiation therapy
Ngo, S. D., Oxley, E. P., Ghisi, M., Garwood, M. M., McKenzie, M. D., Mitchell, H. L., Kanellakis, P., Susanto, O., Hickey, M. J., Perkins, A. C., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26849-w · Cited by 17
Differentiating Inhibition Selectivity and Binding Affinity of Isocitrate Dehydrogenase 1 Variant Inhibitors
Liu, S., Abboud, M. I., Mikhailov, V. A., Liu, X., Reinbold, R., & Schofield, C. J. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00203 · Cited by 18
The Interplay between Dysregulated Metabolism and Epigenetics in Cancer
Bassal, M. A. (2023) · Biomolecules · doi:10.3390/biom13060944 · Cited by 19
Enasidenib in acute myeloid leukemia: clinical development and perspectives on treatment
Reed, D. R., Elsarrag, R. Z., Morris, A., & Keng, M. K. (2019) · Cancer Management and Research · doi:10.2147/cmar.s162784 · Cited by 18
“Enasidenib demonstrated a dosedependent survival benefit in xenograft mice compared to mice treated with cytarabine and demonstrated dosedependent reduction in R-2-HG, reduction in bone marrow blasts, as well as differentiation into mature granulocytes without impacting the IDH2 allele frequency.(15)”
BackgroundInfluential
Targeting IDH Mutations in AML: Wielding the Double-edged Sword of Differentiation
Becker, J. S., & Fathi, A. T. (2020) · Current Cancer Drug Targets · doi:10.2174/1568009620666200424145622 · Cited by 18
Advances in the Immunotherapeutic Potential of Isocitrate Dehydrogenase Mutations in Glioma
Tang, F. R., Pan, Z., Wang, Y., Lan, T., Wang, M., Li, F., Quan, W., Liu, Z., Wang, Z., & Li, Z. (2022) · Neuroscience Bulletin · doi:10.1007/s12264-022-00866-1 · Cited by 18
“The efficacy of AG-221 has been well studied in a primary human AML xenograft model with an IDH2 mutation.”
BackgroundInfluential
Understanding and Targeting Metabolic Vulnerabilities in Acute Myeloid Leukemia: An Updated Comprehensive Review
Addanki, S., Kim, L. E., & Stevens, A. M. (2025) · Cancers · doi:10.3390/cancers17081355 · Cited by 18
Epigenetic Therapies in Melanoma—Targeting DNA Methylation and Histone Modification
Țigu, A. B., Ivancuta, A., Uhl, A., Sabo, A. C., Nistor, M., Mureșan, X. M., Cenariu, D., Timis, T., Diculescu, D. M., & Gulei, D. (2025) · Biomedicines · doi:10.3390/biomedicines13051188 · Cited by 17
“Inhibition of these enzymes results in epigenetic changes and blocks cellular differentiation [135].”
Reprogramming Carbohydrate Metabolism in Cancer and Its Role in Regulating the Tumor Microenvironment
Adhikari, S., Guha, D., Mohan, C., Mukherjee, S., Tyler, J. K., & Das, C. (2022) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-031-07634-3_1 · Cited by 19
Mutated Isocitrate Dehydrogenase (mIDH) as Target for PET Imaging in Gliomas
Neumaier, F., Zlatopolskiy, B. D., & Neumaier, B. (2023) · Molecules · doi:10.3390/molecules28072890 · Cited by 17
Biomimetic Synthesis and Chemical Proteomics Reveal the Mechanism of Action and Functional Targets of Phloroglucinol Meroterpenoids
Bracken, A. K., Gekko, C. E., Suss, N. O., Lueders, E. E., Cui, Q., Fu, Q., Lui, A. C. W., Anderson, E. T., Zhang, S., & Abbasov, M. E. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.3c10741 · Cited by 16
The Impact of the Cellular Origin in Acute Myeloid Leukemia: Learning From Mouse Models
Fisher, J. N., Kalleda, N., Stavropoulou, V., & Schwaller, J. (2019) · HemaSphere · doi:10.1097/hs9.0000000000000152 · Cited by 19
Discovery of novel enasidenib analogues targeting inhibition of mutant isocitrate dehydrogenase 2 as antileukaemic agents
Khalil, A. F., El-Moselhy, T. F., El-Bastawissy, E. A., Abdelhady, R., Younis, N. S., & El‐Hamamsy, M. H. (2023) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2022.2157411 · Cited by 17
“As disclosed cocrystal structure of enasidenib with IDH2 R140Q (PDB ID: 5I96), Enasidenib binding is anchored by multiple hydrogen bonds (H-bonds) formed with Q316 and many hydrophobic interactions 24 .”
BackgroundInfluential
Optimizing Next-Generation AML Therapy: Activity of Mutant IDH2 Inhibitor AG-221 in Preclinical Models
Thomas, D., & Majeti, R. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0270 · Cited by 16
“Two articles in this issue of Cancer Discovery from Agios Pharmaceuticals in collaboration with INSERM (6) and from the laboratories of Ross Levine and Ari Melnick (7) use patient-derived xenografts and genetically engineered mouse models to investigate how this first-in-class epigenetic targeted therapy may be harnes…”
Background
Quantitative analysis of enasidenib in dried blood spots of mouse blood using an increased‐sensitivity LC–MS/MS method: Application to a pharmacokinetic study
Dittakavi, S., Jat, R. K., & Mullangi, R. (2019) · Biomedical Chromatography · doi:10.1002/bmc.4491 · Cited by 16
Abundance of d ‐2‐hydroxyglutarate in G2/M is determined by FOXM1 in mutant IDH1‐expressing cells
Kancharana, B., Katragunta, K., Sarma, U. M., & Jain, N. (2019) · FEBS Letters · doi:10.1002/1873-3468.13500 · Cited by 16
KDM4 inhibitor SD49-7 attenuates leukemia stem cell via KDM4A/MDM2/p21CIP1 axis
Li, Y., Wang, C., Gao, H., Gu, J., Zhang, Y., Zhang, Y., Xie, M., Cheng, X., Yang, M. S., Zhang, W., et al. (2022) · Theranostics · doi:10.7150/thno.71460 · Cited by 16
“Thus far, several epigenetic drugs with good efficacy have entered clinical trials, including the IDH inhibitor AG-221 [36], BET inhibitor OTX015 [37], HDAC inhibitor pracinostat [38], LSD1 inhibitor GSK2879552 [39], and DOT1L inhibitor pinometostat [40].”
Background
P300/CBP‐associated factor regulates transcription and function of isocitrate dehydrogenase 2 during muscle differentiation
Savoia, M., Cencioni, C., Mori, M., Atlante, S., Zaccagnini, G., Devanna, P., Marcotullio, L. D., Botta, B., Martelli, F., Zeiher, A. M., et al. (2018) · The FASEB Journal · doi:10.1096/fj.201800788r · Cited by 16
“The structure of the hIDH2 homodimer (PDB identification: 5SVN) (32) was used as a template to build the initial structure by molecular replacement with the high-resolution structure of monomeric hIDH2 (PBD identification: 5I95) (33).”
Method
Isocitrate Dehydrogenase Mutations in Cancer: Mechanisms of Transformation and Metabolic LiabilityPreprint
Gunn, K., & Losman, J.-A. (2024) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041537 · Cited by 16
Deciphering the multifaceted roles and clinical implications of 2-hydroxyglutarate in cancer
Hao, J., Huang, Z., Zhang, S., Song, K., Wang, J., Gao, C., Fang, Z., & Zhang, N. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107437 · Cited by 15
Ten‐Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy
Liang, J., Na, X., Meng, L., He, L., Shu, T., Fang, Y., Zhang, B., Zhao, Z., Guo, C., Li, J., et al. (2025) · MedComm · doi:10.1002/mco2.70245 · Cited by 15
The epigenetic dysfunction underlying malignant glioma pathogenesis
Dharmaiah, S., & Huse, J. T. (2022) · Laboratory Investigation · doi:10.1038/s41374-022-00741-7 · Cited by 17
Challenges for the development of mutant isocitrate dehydrogenases 1 inhibitors to treat glioma
Wang, Q.-X., Zhang, P.-Y., Li, Q., Tong, Z., Yu, S., Yu, Y., Yu, Y., Ding, N., Leng, X.-J., Chang, L., et al. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115464 · Cited by 15
Enasidenib treatment in two individuals with D-2-hydroxyglutaric aciduria carrying a germline IDH2 mutation
Geoerger, B., Schiff, M., Penard‐Lacronique, V., Darín, N., Saad, S.-M., Duchon, C., Lamazière, A., Desmons, A., Pontoizeau, C., Berlanga, P., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02382-9 · Cited by 15
Self-citation
Mechanisms of Resistance to Small Molecules in Acute Myeloid Leukemia
Lang, T. J. L., Damm, F., Bullinger, L., & Frick, M. (2023) · Cancers · doi:10.3390/cancers15184573 · Cited by 16
“Inhibition of IDH1 or IDH2 in the presence of an oncogenic mutation, therefore, suppresses the production of the oncometabolite 2-HG and induces hematopoietic differentiation, making pharmacologic IDH inhibition a highly attractive therapeutic approach [70,71].”
Background
The Elements of Translational Chemical Biology
Copeland, R. A., & Boriack‐Sjodin, P. A. (2017) · Cell chemical biology · doi:10.1016/j.chembiol.2017.11.003 · Cited by 15
Bridging Cancer Biology with the Clinic: Comprehending and Exploiting IDH Gene Mutations in Gliomas
Romanidou, O., Kotoula, V., & Fountzilas, G. (2018) · Cancer Genomics & Proteomics · doi:10.21873/cgp.20101 · Cited by 15
Therapeutic targeting of chromatin alterations in leukemia and solid tumors
Perner, F., Berg, T., Sasca, D., Mersiowsky, S., Gadrey, J. Y., Thomas, J. M., Kühn, M. W. M., & Lübbert, M. (2025) · International Journal of Cancer · doi:10.1002/ijc.35389 · Cited by 16
MiRNA-142-3P and FUS can be Sponged by Long Noncoding RNA DUBR to Promote Cell Proliferation in Acute Myeloid Leukemia
Yin, Z., Shen, H., Gu, C., Zhang, M. Q., Liu, Z., Huang, J., Zhu, Y., Zhong, Q., Huang, Y., Wu, F., et al. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.754936 · Cited by 14
“Recently, some AMLmolecular biology-based novel treatments are proposed, yet the prognosis of disease is still dismal (Yen et al., 2017).”
Background
Genetic mutations affecting mitochondrial function in cancer drug resistance
Lee, C., Park, S., & Yoon, S. K. (2023) · Genes & Genomics · doi:10.1007/s13258-022-01359-1 · Cited by 15
A personalized medicine approach identifies enasidenib as an efficient treatment for IDH2 mutant chondrosarcoma
Rey, V., Tornín, J., Alba‐Linares, J. J., Robledo, C., Murillo, D., Rodríguez, A., Gallego, B., Huergo, C., Viera, C., Braña, A., et al. (2024) · EBioMedicine · doi:10.1016/j.ebiom.2024.105090 · Cited by 16
“25,26 IDH anti-mutant treatments may also represent a therapeutic alternative for chondrosarcomas, however, the effect of these compounds in this type of tumours has been barely explored.”
BackgroundResult
Recent Developments in Differentiation Therapy of Acute Myeloid Leukemia
Testa, U., Castelli, G., & Pelosi, E. (2025) · Cancers · doi:10.3390/cancers17071141 · Cited by 15
“Enasidenib potently inhibited 2HG production by IDH2 R140Q homodimer and IDH2 R140Q/WT heterodimer and displayed favorable pharmaceutical properties such as solubulity, slow clearance and oral bioavailability [50].”
Influential
CHIRAL, FLUORINE-CONTAINING PHARMACEUTICALS
Han, J., Wzorek, A., Dhawan, G., Zhang, W., Sorochinsky, A. E., Baecker, D., Ono, T., Klika, K. D., & Soloshonok, V. A. (2025) · Ukrainian Chemistry Journal · doi:10.33609/2708-129x.91.2.2025.55-90 · Cited by 14
All-Trans Retinoic Acid Synergizes with Enasidenib to Induce Differentiation of IDH2-Mutant Acute Myeloid Leukemia Cells
Kim, Y., Jeung, H.-K., Cheong, J., Song, J., Bae, S. H., Lee, J. I., & Min, Y. H. (2020) · Yonsei Medical Journal · doi:10.3349/ymj.2020.61.9.762 · Cited by 16
“AG-221 exhibits excellent pharmaceutical characteristics, including proper solubility, low clearance, and good oral bioavailability, and powerfully inhibits 2-HG production by both the IDH2/R140Q-WT heterodimer and IDH2/R140Q homodimer.(29) Our data indicated that in IDH2-mutant AML cells, IDH2/R140Q expression in the…”
BackgroundResult
Inhibitor potency varies widely among tumor-relevant human isocitrate dehydrogenase 1 mutants
Matteo, D. A., Wells, G. A., Luna, L. A., Grunseth, A. J., Zagnitko, O. P., Scott, D. A., Hoang, A. D., Luthra, A., Swairjo, M. A., Schiffer, J. M., et al. (2018) · Biochemical Journal · doi:10.1042/bcj20180424 · Cited by 14
“Agios Pharmaceuticals has recently received FDA approval for mutant IDH1 [19,20] and IDH2 inhibitors [21,22].”
Background
Lack of evidence for substrate channeling or flux between wildtype and mutant isocitrate dehydrogenase to produce the oncometabolite 2-hydroxyglutarate
Dexter, J. P., Ward, P. S., Dasgupta, T., Hosios, A. M., Gunawardena, J., & Heiden, M. G. V. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.004278 · Cited by 14
An acidic residue buried in the dimer interface of isocitrate dehydrogenase 1 (IDH1) helps regulate catalysis and pH sensitivity
Luna, L. A., Lesecq, Z., White, K. A., Hoang, A. D., Scott, D. A., Zagnitko, O. P., Bobkov, A. A., Barber, D. L., Schiffer, J. M., Isom, D. G., et al. (2020) · Biochemical Journal · doi:10.1042/bcj20200311 · Cited by 13
Mutant Idh2 Cooperates with a NUP98-HOXD13 Fusion to Induce Early Immature Thymocyte Precursor ALL
Goldberg, L., Negi, V., Chung, Y. J., Onozawa, M., Zhu, Y. J., Walker, R. L., Pierce, R. M., Patel, D. P., Krausz, K. W., Gonzalez, F. J., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-1027 · Cited by 12
Targeting mitochondrial metabolism in acute myeloid leukemia
Rex, M., Williams, R., Birsoy, K., llman, M. S. T., & Stahl, M. (2021) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2021.1992759 · Cited by 13
Translational and Clinical Relevance of PDX‐Derived Organoid Models in Oncology Drug Discovery and Development
Kumari, R., Xu, X., & Li, H. (2022) · Current Protocols · doi:10.1002/cpz1.431 · Cited by 13
“In addition, many PDXs have been extensively tested with various investigational therapies (Jiang et al., 2019; Plenker et al., 2017; Yen et al., 2017), including in the format of MCTs (Chen et al., 2015; Iwai et al., 2019; Janes et al., 2018; Zhang et al., 2013; Zhu et al., 2018).”
Background
Transgenic IDH2R172K and IDH2R140Q zebrafish models recapitulated features of human acute myeloid leukemia
Wang, D., Zheng, L., Cheng, B. Y.-L., Sin, C., Li, R., Tsui, S. P., Yi, X., Ma, A. C. H., He, B. L., Leung, A. Y. H., et al. (2023) · Oncogene · doi:10.1038/s41388-023-02611-y · Cited by 13
“As proof-ofprinciple, both zebrafish embryos and adults carrying FLT3IDH2 and FLT3IDH2 mutations responded to quizartinib/gilteritinib, and enasidenib, which were effective agents for FLT3 [34, 35] and IDH2 mutant AML [36, 37].”
Background
Electrochemical Nanoreactor Provides a Comprehensive View of Isocitrate Dehydrogenase Cancer‐drug Kinetics
Herold, R. A., Schofield, C. J., & Armstrong, F. A. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202309149 · Cited by 12
Crosstalk between DNA methylation and hypoxia in acute myeloid leukaemia
Humphries, S., Bond, D. R., Germon, Z. P., Keely, S., Enjeti, A. K., Dun, M. D., & Lee, H. J. (2023) · Clinical Epigenetics · doi:10.1186/s13148-023-01566-x · Cited by 15
“By reducing 2-HG production, IDH inhibitors can trigger epigenetic reprogramming and restoration of myeloid differentiation in AML [108, 109].”
Background
Therapeutic biomarkers in acute myeloid leukemia: functional and genomic approaches
Bhatia, K. S., Sandhu, V., Wong, M. H., Iyer, P., & Bhatt, S. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1275251 · Cited by 13
Differentiation syndrome associated with treatment with IDH2 inhibitor enasidenib: pooled analysis from clinical trials
Montesinos, P., Fathi, A. T., de Botton, S., Stein, E. M., Zeidan, A. M., Zhu, Y., Prébet, T., Vigil, C. E., Bluemmert, I., Yu, X., et al. (2024) · Blood Advances · doi:10.1182/bloodadvances.2023011914 · Cited by 13
Synergizing metabolomics and artificial intelligence for advancing precision oncology
Xu, Y., Jiang, X.-J., & Hu, Z. (2025) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2025.01.016 · Cited by 14
Self-citation
An evaluation of enasidenib for the treatment of acute myeloid leukemia
Principe, M. I. D., Paterno, G., Palmieri, R., Maurillo, L., Buccisano, F., & Venditti, A. (2019) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2019.1654456 · Cited by 14
“Bone marrow blasts from patients with mutant IDH2 AML exposed to enasidenib transform into mature, functioning neutrophils, confirming that the mature cells evolved from the IDH2 mutant blasts [45,46].”
Background
Rapid chiral discrimination of oncometabolite dl ‐2‐hydroxyglutaric acid using derivatization and field asymmetric waveform ion mobility spectrometry/mass spectrometry
Fukui, S., Sugiyama, E., Mizuno, H., Sakane, I., Asakawa, D., Saikusa, K., Nishiya, Y., Amano, Y., Takahara, K., Higo, D., et al. (2021) · Journal of Separation Science · doi:10.1002/jssc.202100350 · Cited by 13
Isocitrate dehydrogenase 2 inhibitor enasidenib synergizes daunorubicin cytotoxicity by targeting aldo-keto reductase 1C3 and ATP-binding cassette transporters
Morell, A., Budagaga, Y., Vagiannis, D., Zhang, Y. X., Laštovičková, L., Novotná, E., Haddad, A., Haddad, M., Portillo, R., Hofman, J., et al. (2022) · Archives of Toxicology · doi:10.1007/s00204-022-03359-2 · Cited by 12
“In 2017, enasidenib (ENA; trade name Idhifa) was the first selective inhibitor of IDH2 mutants (R140Q and R172K) approved by the FDA for relapsed/refractory IDH2-mutated AML (Yen et al.”
Background
Transient-State Analysis of Human Isocitrate Dehydrogenase I: Accounting for the Interconversion of Active and Non-Active Conformational States
Roman, J. V., Melkonian, T. R., Silvaggi, N. R., & Moran, G. R. (2019) · Biochemistry · doi:10.1021/acs.biochem.9b00518 · Cited by 13
Targeting DNA repair in gliomas
Beckta, J. M., Bindra, R. S., & Chalmers, A. J. (2019) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000760 · Cited by 13
“It has demonstrated a potent ability to deplete 2hydroxyglutarate both in vitro and in vivo [70], and a phase I/II study published in 2017 demonstrated clinical efficacy in relapsed or refractory AML [71].”
Background
Response Kinetics and Clinical Benefits of Nonintensive AML Therapies in the Absence of Morphologic Response
Stein, E. M., Dinardo, C. D., Pollyea, D. A., & Schuh, A. C. (2019) · Clinical Lymphoma Myeloma & Leukemia · doi:10.1016/j.clml.2019.11.017 · Cited by 13
Advances in the pathogenesis and therapeutic strategies of angioimmunoblastic T-cell lymphoma
Zhang, Q., Yin, L., Lai, Q., Zhao, Y., & Peng, H. (2023) · Clinical and Experimental Medicine · doi:10.1007/s10238-023-01197-9 · Cited by 12
Multivariate analysis of metabolic state vulnerabilities across diverse cancer contexts reveals synthetically lethal associations
Abecunas, C., Kidd, A. D., Jiang, Y., Zong, H., & Fallahi‐Sichani, M. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114775 · Cited by 14
Current development and future perspective of IDH1 inhibitors in cholangiocarcinoma
Adeva, J. (2021) · Liver Cancer International · doi:10.1002/lci2.43 · Cited by 12
Druggable Metabolic Vulnerabilities Are Exposed and Masked during Progression to Castration Resistant Prostate Cancer
Choi, S. Y. C., Ribeiro, C. F., Wang, Y. Z., Loda, M. F., Plymate, S. R., & Uo, T. (2022) · Biomolecules · doi:10.3390/biom12111590 · Cited by 13
IDH mutation and cancer stem cell
Zhang, Y., Liu, Y., Lang, F., & Yang, C. (2022) · Essays in Biochemistry · doi:10.1042/ebc20220008 · Cited by 11
The curious case of IDH mutant acute myeloid leukaemia: biochemistry and therapeutic approaches
Gruber, E., & Kats, L. M. (2023) · Biochemical Society Transactions · doi:10.1042/bst20230017 · Cited by 11
CRISPR Dependency Screens in Primary Hematopoietic Stem Cells Identify KDM3B as a Genotype-specific Vulnerability in IDH2 - and TET2 -mutant Cells
Waarts, M. R., Mowla, S., Boileau, M., Benitez, A. R. M., Sango, J., Bagish, M., Fernández-Maestre, I., Shan, Y., Eisman, S. E., Park, Y. C., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-1092 · Cited by 13
Epigenetic-based differentiation therapy for Acute Myeloid Leukemia
José‐Eneriz, E. S., Gimenez-Camino, N., Rabal, O., Gárate, L., Miranda, E., Gómez-Echarte, N., Garcı́a, F., Charalampopoulou, S., Sáez, E., Vilas‐Zornoza, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49784-y · Cited by 11
“…Panobinostat treatment of a mouse model of AML bearing the AML1/ETO fusion triggered terminal myeloid dif-ferentiationwitharemarkableanti-leukemicresponse 19 ,andtreatment with small-molecule inhibitors against IDH1/2 also induced myeloid differentiation in AML models with mutant IDH1/2 20,21 .”
Background
Discovery of HMPL-306 (Ranosidenib), a New Potent and Selective Dual Inhibitor of Mutant IDH1 and 2 in Clinical Development for Cancer Treatment
Xiao, K., Zhang, Z., Wu, Y., Li, G., Chen, J., Ren, Y., Yang, N., Zhou, J., Zhang, W., Wang, J., et al. (2025) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.4c00625 · Cited by 11
Integration of reduced graphene oxide, Fe-MOF and NiCe2O4 nanocomposite for high-performance energy and electrochemical sensing applications
Sunitha, A., Chennakesavulu, K., Kumar, A., Afzal, A. M., Kanabar, B. K., Rekha, M. M., Pradhan, P., Choukaier, D., Oza, A. D., Diab, M. A., et al. (2025) · Diamond and Related Materials · doi:10.1016/j.diamond.2025.112530 · Cited by 11
Identification of new IDH2R140Q inhibitors by discriminatory analysis‐based molecular docking and biological evaluation
Chen, X., Wu, X., Gao, J., Ying, H., Dong, X., Che, J., & Shen, Z. (2020) · Archiv der Pharmazie · doi:10.1002/ardp.202000063 · Cited by 12
The evolution of epigenetic therapy in myelodysplastic syndromes and acute myeloid leukemia
Gonzalez‐Lugo, J. D., Chakraborty, S., Verma, A., & Shastri, A. (2020) · Seminars in Hematology · doi:10.1053/j.seminhematol.2020.12.003 · Cited by 11
From Metabolism to Genetics and Vice Versa: The Rising Role of Oncometabolites in Cancer Development and Therapy
Gregorio, E. D., Miolo, G., Saorin, A., Steffan, A., & Corona, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115574 · Cited by 11
“FDA ap‐ proval IDH2 Reversible, allosteric non‐compet‐ itive inhibition via stabilization of the mutated IDH non‐catalytic open conformation that prevents R‐2HG formation [242].”
BackgroundInfluential
Targeting mitochondrial homeostasis as a cancer treatment strategy: current status and future prospects
Zhong, H., Pan, R., Ouyang, Y., Xiao, T., Gu, W., Yang, H., Wang, H., Li, H., Peng, T., & Chen, P. (2026) · Molecular Cancer · doi:10.1186/s12943-026-02571-3 · Cited by 13
“…IDH inhibition by AGI-5198 reduces (R)−2-HG formation, causing epigenetic dysregulation and a block in cellular differentiation [274]; enasidenib and vorasidenib are FDA-approved for the treatment of acute myelogenous leukemia and glioma with IDH2 and IDH1/2 mutations, respectively [257, 275].”
Self-citation
Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies
Giercuszkiewicz-Haśnik, K., MORAK-MŁODAWSKA, B. I., & Jeleń, M. (2026) · Molecules · doi:10.3390/molecules31071195 · Cited by 14
Traditional Chinese medicine for acute myelocytic leukemia therapy: exploiting epigenetic targets
Gao, X., Zuo, X., Min, T., Wan, Y., He, Y., & Jiang, B. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1388903 · Cited by 10
A decade of approved first-in-class small molecule orphan drugs: Achievements, challenges and perspectives
Gu, J., Wu, Q., Zhang, Q., You, Q., & Wang, L. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114742 · Cited by 11
Enzymology on an Electrode and in a Nanopore: Analysis Algorithms, Enzyme Kinetics, and Perspectives
Shumyantseva, V. V., Kuzikov, A. V., Masamrekh, R. A., Filippova, T. A., Koroleva, P. I., Agafonova, L. E., Bulko, T. V., & Archakov, A. I. (2022) · BioNanoScience · doi:10.1007/s12668-022-01037-2 · Cited by 10
Optimal Bayesian Filtering for Biomarker Discovery: Performance and Robustness
pour, A. F., & Dalton, L. A. (2018) · IEEE Transactions on Computational Biology and Bioinformatics · doi:10.1109/tcbb.2018.2858814 · Cited by 10
“Furthermore, [41] states that inAMLpatients “Treatment of TF-1 cells with erythropoietin (EPO) induces expression of the genes hemoglobin alpha 1 and 2 (HBA1/2),” and “on AG-221 treatment, dose-dependent increases in KLF1 and HBA1/2 expression were seen in IDH2 cells.”
Background
Structure-based design, synthesis and bioactivity evaluation of macrocyclic inhibitors of mutant isocitrate dehydrogenase 2 (IDH2) displaying activity in acute myeloid leukemia cells
Che, J., Huang, F., Zhang, M., Xu, G., Qu, B., Gao, J., Chen, B., Zhang, J., Ying, H., Hu, Y., et al. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112491 · Cited by 10
Cutting Edge Molecular Therapy for Acute Myeloid Leukemia
Miyamoto, K., & Minami, Y. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21145114 · Cited by 11
“Enasidenib inhibits both R140Q- and R172K-mutated IDH2 [41].”
BackgroundInfluential
Effects of cancer-associated point mutations on the structure, function, and stability of isocitrate dehydrogenase 2
Chen, X. '., Yang, P., Qiao, Y., Ye, F., Wang, Z., Xu, M., Han, X., Song, L., Wu, Y., & Ou, W. (2022) · Scientific Reports · doi:10.1038/s41598-022-23659-y · Cited by 10
Prediction of metabolites associated with somatic mutations in cancers by using genome-scale metabolic models and mutation data
Lee, G., Lee, S. M., Lee, S., Jeong, C. W., Song, H., Lee, S. Y., Yun, H., Koh, Y., & Kim, H. U. (2024) · Genome biology · doi:10.1186/s13059-024-03208-8 · Cited by 9
“Among the final six MG pairs supported with the metabolome data, target metabolites paired with DNMT3A , IDH , IDH2 , or NRAS showed AUC values greater than 0.7 [34, 35] (Fig.”
BackgroundInfluential
Emerging DNA Methylome Targets in FLT3-ITD-Positive Acute Myeloid Leukemia: Combination Therapy with Clinically Approved FLT3 Inhibitors
Tecik, M., & Adan, A. (2024) · Current Treatment Options in Oncology · doi:10.1007/s11864-024-01202-7 · Cited by 9
“Enasidenib is a selective allosteric inhibitor of IDH2 which binds to open conformation of the enzyme and stabilizes it, thereby blocking the conversion of a-KG to 2-HG [223].”
Background
Allostery Illuminated: Harnessing AI and Machine Learning for Drug Discovery
Blanco, M.-J., Buskes, M. J., Govindaraj, R. G., Ipsaro, J. J., Prescott-Roy, J., & Padyana, A. K. (2024) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.4c00260 · Cited by 9
Self-citation
Metabolic functions of misunderstood D-2-hydroxyglutarate
Liu, Y., Kang, Z., Zhang, W., Ma, C., Xu, P., & Gao, C. (2024) · The Innovation Life · doi:10.59717/j.xinn-life.2024.100101 · Cited by 10
IDH-mutant gliomas in children and adolescents - from biology to clinical trials
Evans, L., Trinder, S. M., Dodgshun, A. J., Eisenstat, D. D., Whittle, J. R., Hansford, J. R., & Valvi, S. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2024.1515538 · Cited by 10
CD44-mediated metabolic rewiring is a targetable dependency of IDH-mutant leukemia
Lyu, J., Liu, Y., Liu, N., Vu, H. S., Cai, F., Cao, H., Kaphle, P., Wu, Z., Botten, G. A., Zhang, Y., et al. (2025) · Blood · doi:10.1182/blood.2024027207 · Cited by 10

Authors: Yen, K., Travins, J., Wang, F., David, M. D., Artin, E., Straley, K., Padyana, A., Gross, S., DeLaBarre, B., Tobin, E., Chen, Y., Nagaraja, R., Choe, S., Jin, L., Konteatis, Z., Cianchetta, G., Saunders, J. O., Salituro, F. G., Quivoron, C., Opolon, P., Bawa, O., Saada, V., Paci, A., Broutin, S., Bernard, O. A., de Botton, S., Marteyn, B. S., Pilichowska, M., Xu, Y., Fang, C., Jiang, F., Wei, W., Jin, S., Silverman, L., Liu, W., Yang, H., Dang, L., Dorsch, M., Penard-Lacronique, V., Biller, S. A., & Su, S.-S. M.
Affiliations: Agios Pharmaceuticals (United States) (US)
Inserm (FR)
1Agios Pharmaceuticals, Inc., Cambridge, Massachusetts.
Université Paris-Saclay (FR)
6Service de Pharmacologie, Département de Biologie et Pathologie Médicales, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
2INSERM U1170, Villejuif, France.
Tufts Medical Center (US)
11ShangPharma, Shanghai, China.
Viva Biotech (China) (CN)
Corresponding author: Su, Shin-San Michael
ORCID: Yen, Katharine
Wang, Fang
David, Muriel D.
Padyana, Anil
Tobin, Erica
Chen, Yue
Choe, Sung
Jin, Lei
Konteatis, Zenon
Salituro, Francesco G.
Quivoron, Cyril
Opolon, Paule
Bawa, Olivia
Saada, Véronique
Broutin, Sophie
Bernard, Olivier A.
Marteyn, Benoît S.
Pilichowska, Monika
Jiang, Fan
Wei, Wentao
Liu, Wei
Yang, Hua
Dang, Lenny
Venue: Cancer Discovery
Publisher: American Association for Cancer Research (AACR)
Published: 2017-04-30
Volume: 7
Issue: 5
Pages: 478-493
ISSN: 2159-8274 (ISSN-L)
2159-8290
DOI: 10.1158/2159-8290.cd-16-1034
OpenAlex: W2588385654
Cited by: 471
References: 52
Citations by year: 2026: 35 · 2025: 47 · 2024: 51 · 2023: 46 · 2022: 48 · 2021: 78 · 2020: 55 · 2019: 37 · 2018: 51 · 2017: 23
FWCI: 34.99
Type: journal article
Language: en
Open access: closed
Locations: Cancer Discovery (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (INCa-DGOS-Inserm_6043 and INCa 2012-1-RT-09)
Association pour la Recherche sur le Cancer (SL220130607089)
Institut National Du Cancer (INCa-DGOS_5733)
Topics: Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: IDH2 inhibitors, acute myeloid leukemia, IDH2 mutation, 2-hydroxyglutarate, oncometabolites, hematopoietic differentiation, TET methylcytosine dioxygenases, histone demethylase, xenograft mouse model
MeSH terms: Aminopyridines, Animals, Antineoplastic Agents, Humans, Isocitrate Dehydrogenase, Mutation, Triazines, Leukemia, Myeloid, Acute, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks