ArticleCancer cell2015
CHZ868, a Type II JAK2 Inhibitor, Reverses Type I JAK Inhibitor Persistence and Demonstrates Efficacy in Myeloproliferative Neoplasms.
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Article in Cancer cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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95citing papers in PubMed
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Who cites it
95 citing papers in PubMed, 152 citations in OpenAlex.
- Review
- Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications.Nature reviews. Drug discovery · 2026Review
- A Scalable Design for Proximity-Inducing Molecules.bioRxiv : the preprint server for biology · 2026Article
- Article
- The Immunoregulatory and Hematopoietic Effects of Momelotinib in a Murine Bone Marrow Failure Model.Journal of clinical laboratory analysis · 2026Article
- Breast cancer cell coculture induces normal lung fibroblast transition to CAFs, promoting tumor cell dormancy and therapy resistance.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Ruxolitinib mediated paradoxical JAK2 hyperphosphorylation is due to the protection of activation loop tyrosines from phosphatases.Leukemia · 2025Article
- STAT1-mediated interferon signatures are associated with preclinical JAK inhibitor sensitivity in T-ALL.Blood · 2025Article
- Targeted Therapies in Myelofibrosis: Present Landscape, Ongoing Studies, and Future Perspectives.American journal of hematology · 2025Review
- Recent advances and future perspectives in small molecule JAK2 inhibitors.Future medicinal chemistry · 2025Review
- Selective JAK2 pathway inhibition enhances anti-leukemic functionality in CD19 CAR-T cells.Cancer immunology, immunotherapy : CII · 2025Article
- The Ongoing Challenges of Managing Cytopenic Myelofibrosis in 2025: The Emergence of Non-JAK Inhibitor Therapies.Blood and lymphatic cancer : targets and therapy · 2025Review
- Investigational drugs in early phase trials for myelofibrosis.Expert opinion on investigational drugs · 2024Review
- Myeloproliferative neoplasms in the adolescent and young adult population: A comprehensive review of the literature.British journal of haematology · 2024Review
- SHP2 inhibition displays efficacy as a monotherapy and in combination with JAK2 inhibition in preclinical models of myeloproliferative neoplasms.American journal of hematology · 2024Article
- Jak2V617F Reversible Activation Shows Its Essential Requirement in Myeloproliferative Neoplasms.Cancer discovery · 2024Article
- Tyrosine phosphorylation of CARM1 promotes its enzymatic activity and alters its target specificity.Nature communications · 2024Article
- Development of Resistance to Type II JAK2 Inhibitors in MPN Depends on AXL Kinase and Is Targetable.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Type II mode of JAK2 inhibition and destabilization are potential therapeutic approaches against the ruxolitinib resistance driven myeloproliferative neoplasms.Frontiers in oncology · 2024Article
- Molecular biomarkers of leukemia: convergence-based drug resistance mechanisms in chronic myeloid leukemia and myeloproliferative neoplasms.Frontiers in pharmacology · 2024Review
35 more citing papers are in PubMed but not listed here.
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Authors and funding
38 authors at 7 institutions in 2 countries.
Sara C MeyerHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Matthew D KellerHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Sophia ChiuHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Priya KoppikarHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Olga A GuryanovaHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Franck RapaportHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Ke XuMolecular Cytology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Katia ManovaMolecular Cytology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Dmitry PankovDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Richard J O'ReillyDepartment of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Maria KleppeHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Anna Sophia McKenneyHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Alan H ShihHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Kaitlyn ShankHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jihae AhnHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Eftymia PapalexiHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Barbara SpitzerHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Nick SocciCenter for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Agnes VialeCenter for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Emeline MandonNovartis Institutes for Biomedical Research, Basel 4056, Switzerland.
Nicolas EbelNovartis Institutes for Biomedical Research, Basel 4056, Switzerland.
Rita AndraosNovartis Institutes for Biomedical Research, Basel 4056, Switzerland.
Joëlle RubertNovartis Institutes for Biomedical Research, Basel 4056, Switzerland.
Ernesta DammassaNovartis Institutes for Biomedical Research, Basel 4056, Switzerland.
Vincent RomanetNovartis Institutes for Biomedical Research, Basel 4056, Switzerland.
Arno DölemeyerNovartis Institutes for Biomedical Research, Basel 4056, Switzerland.
Michael ZenderNovartis Institutes for Biomedical Research, Basel 4056, Switzerland.
Melanie HeinleinNovartis Institutes for Biomedical Research, Basel 4056, Switzerland.
Raajit RampalHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Rona Singer WeinbergNew York Blood Center, New York, NY 10065, USA.
Ronald HoffmanDepartment of Medicine, Mount Sinai Hospital, New York, NY 10029, USA.
William R SellersNovartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
Francesco HofmannNovartis Institutes for Biomedical Research, Basel 4056, Switzerland.
Masato MurakamiNovartis Institutes for Biomedical Research, Basel 4056, Switzerland.
Fabienne BaffertNovartis Institutes for Biomedical Research, Basel 4056, Switzerland.
Christoph GaulNovartis Institutes for Biomedical Research, Basel 4056, Switzerland.
Thomas RadimerskiNovartis Institutes for Biomedical Research, Basel 4056, Switzerland. Electronic address: thomas.radimerski@novartis.com.
Ross L LevineHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: leviner@mskcc.org.
Memorial Sloan Kettering Cancer Center · USNovartis Institutes for BioMedical ResearchNovartis (Switzerland) · CHMolecular Oncology (United States) · USMount Sinai Hospital · USNew York Blood Center · USNovartis (United States) · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MTissue BankP01CA108671 · NCI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI Ronald Hoffman · 2006 to 2026
$82.0MT LYMPHOCYTE SUBSET FUNCTION POST-TRANSPLANTATIONP01CA023766 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI GIRALT, SERGIO A · 1985 to 2023
$59.0MWeill Cornell/Rockefeller/Sloan-Kettering MST ProgramT32GM007739 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI HSU, KATHARINE C · 1985 to 2023
$51.1MMolecular Pathogenesis and Therapy of ET and PMFR01CA151949 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI LEVINE, ROSS L · 2010 to 2016
$2.3MGenomic profiling and development of murine models of transformation of MPNsK08CA188529 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI RAMPAL, RAAJIT · 2014 to 2018
$891kBiologic and therapeutic relevance of DNMT3A mutations in acute myeloid leukemiaK99CA178191 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI GURYANOVA, OLGA A · 2013 to 2014
$196kModeling Transformation: Myeloproliferative Neoplasms to Acute Myeloid LeukemiaF30CA183497 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI MCKENNEY, ANNA SOPHIA · 2014 to 2017
$193kNCI NIH HHS 1K99CA178191NCI NIH HHS 1R01CA151949-01NCI NIH HHS 5F30CA183497NCI NIH HHS F30 CA183497NCI NIH HHS K08 CA188529NCI NIH HHS K99 CA178191NCI NIH HHS P01 CA023766NCI NIH HHS P01 CA108671NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA151949NIGMS NIH HHS T32 GM007739NIGMS NIH HHS T32GM007739
Abstract
Although clinically tested JAK inhibitors reduce splenomegaly and systemic symptoms, molecular responses are not observed in most myeloproliferative neoplasm (MPN) patients. We previously demonstrated that MPN cells become persistent to type I JAK inhibitors that bind the active conformation of JAK2. We investigated whether CHZ868, a type II JAK inhibitor, would demonstrate activity in JAK inhibitor persistent cells, murine MPN models, and MPN patient samples. JAK2 and MPL mutant cell lines were sensitive to CHZ868, including type I JAK inhibitor persistent cells. CHZ868 showed significant activity in murine MPN models and induced reductions in mutant allele burden not observed with type I JAK inhibitors. These data demonstrate that type II JAK inhibition is a viable therapeutic approach for MPN patients.
Indexed as
AnimalsAntineoplastic AgentsBenzamidesCell Line, TumorCell ProliferationHumansJanus Kinase 2MiceMice, Inbred C57BLMolecular Sequence DataMutationMyeloproliferative DisordersProtein Kinase InhibitorsPyrimidinesReceptors, ThrombopoietinSequence Analysis, RNAAntineoplastic AgentsBenzamidesJAK2 protein, humanJanus Kinase 2MPL protein, humanN-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamideProtein Kinase InhibitorsPyrimidinesReceptors, Thrombopoietin
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