ArticleBlood cancer journal2011
Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms.
Article in Blood cancer journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 45 citations in OpenAlex.
- A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis.Leukemia · 2017Trial
- Recent advances and future perspectives in small molecule JAK2 inhibitors.Future medicinal chemistry · 2025Review
- JAK2 inhibitors for the treatment of Philadelphia-negative myeloproliferative neoplasms: current status and future directions.Molecular diversity · 2024Review
- Janus Kinases in Leukemia.Cancers · 2021Review
- The role of driver mutations in myeloproliferative neoplasms: insights from mouse models.International journal of hematology · 2020Review
- Targeted therapies for myeloproliferative neoplasms.Biomarker research · 2019Review
- NS-018 reduces myeloma cell proliferation and suppresses osteolysis through inhibition of the JAK2 and Src signaling pathways.Blood cancer journal · 2018Article
- JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders.F1000Research · 2018Review
- Review
- Developmental Therapeutics in Myeloproliferative Neoplasms.Clinical lymphoma, myeloma & leukemia · 2017Review
- Protein kinase small molecule inhibitors for rheumatoid arthritis: Medicinal chemistry/clinical perspectives.World journal of orthopedics · 2014Review
- Effect of NS-018, a selective JAK2V617F inhibitor, in a murine model of myelofibrosis.Blood cancer journal · 2014Article
- Preclinical models for drug selection in myeloproliferative neoplasms.Current hematologic malignancy reports · 2013Review
- JAK2 mutants (e.g., JAK2V617F) and their importance as drug targets in myeloproliferative neoplasms.JAK-STAT · 2013Review
- Sensitivity and resistance of JAK2 inhibitors to myeloproliferative neoplasms.International journal of hematology · 2013Review
- Dysregulation of JAK-STAT pathway in hematological malignancies and JAK inhibitors for clinical application.Biomarker research · 2013Article
- Therapy with JAK2 inhibitors for myeloproliferative neoplasms.Hematology/oncology clinics of North America · 2012Review
- Potential use of STAT3 inhibitors in targeted prostate cancer therapy: future prospects.OncoTargets and therapy · 2012Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant activation of Janus kinase 2 (JAK2) caused by somatic mutation of JAK2 (JAK2V617F) or the thrombopoietin receptor (MPLW515L) plays an essential role in the pathogenesis of myeloproliferative neoplasms (MPNs), suggesting that inhibition of aberrant JAK2 activation would have a therapeutic benefit. Our novel JAK2 inhibitor, NS-018, was highly active against JAK2 with a 50% inhibition (IC(50)) of <1 n, and had 30-50-fold greater selectivity for JAK2 over other JAK-family kinases, such as JAK1, JAK3 and tyrosine kinase 2. In addition to JAK2, NS-018 inhibited Src-family kinases. NS-018 showed potent antiproliferative activity against cell lines expressing a constitutively activated JAK2 (the JAK2V617F or MPLW515L mutations or the TEL-JAK2 fusion gene; IC(50)=11-120 n), but showed only minimal cytotoxicity against most other hematopoietic cell lines without a constitutively activated JAK2. Furthermore, NS-018 preferentially suppressed in vitro erythropoietin-independent endogenous colony formation from polycythemia vera patients. NS-018 also markedly reduced splenomegaly and prolonged the survival of mice inoculated with Ba/F3 cells harboring JAK2V617F. In addition, NS-018 significantly reduced leukocytosis, hepatosplenomegaly and extramedullary hematopoiesis, improved nutritional status, and prolonged survival in JAK2V617F transgenic mice. These results suggest that NS-018 will be a promising candidate for the treatment of MPNs.
Identifiers
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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.