ArticleBlood cancer journal2014
Effect of NS-018, a selective JAK2V617F inhibitor, in a murine model of myelofibrosis.
Article in Blood cancer journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis.Leukemia · 2017Trial
- The Importance of the Pyrazole Scaffold in the Design of Protein Kinases Inhibitors as Targeted Anticancer Therapies.Molecules (Basel, Switzerland) · 2023Review
- Calming the cytokine storm of COVID-19 through inhibition of JAK2/STAT3 signaling.Drug discovery today · 2022Review
- JAK Inhibition for the Treatment of Myelofibrosis: Limitations and Future Perspectives.HemaSphere · 2020Review
- Advances in potential treatment options for myeloproliferative neoplasm associated myelofibrosis.Expert opinion on orphan drugs · 2019Article
- NS-018 reduces myeloma cell proliferation and suppresses osteolysis through inhibition of the JAK2 and Src signaling pathways.Blood cancer journal · 2018Article
- Review
- Developmental Therapeutics in Myeloproliferative Neoplasms.Clinical lymphoma, myeloma & leukemia · 2017Review
- Overview of Transgenic Mouse Models of Myeloproliferative Neoplasms (MPNs).Current protocols in pharmacology · 2017Review
- Rethinking JAK2 inhibition: towards novel strategies of more specific and versatile Janus kinase inhibition.Leukemia · 2017Review
- Three Tyrosine Residues in the Erythropoietin Receptor Are Essential for Janus Kinase 2 V617F Mutant-induced Tumorigenesis.The Journal of biological chemistry · 2017Article
- New Strategies in Myeloproliferative Neoplasms: The Evolving Genetic and Therapeutic Landscape.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Review
- JAK2 inhibition has different therapeutic effects according to myeloproliferative neoplasm development in mice.Journal of cellular and molecular medicine · 2015Article
- A comprehensive review of pacritinib in myelofibrosis.Future oncology (London, England) · 2015Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A single somatic mutation, V617F, in Janus kinase 2 (JAK2) is one of the causes of myeloproliferative neoplasms (MPNs), including primary myelofibrosis, and the JAK2V617F mutant kinase is a therapeutic target in MPN. However, inhibition of wild-type (WT) JAK2 can decrease the erythrocyte or platelet (PLT) count. Our selective JAK2 inhibitor, NS-018, suppressed the growth of Ba/F3 cells harboring JAK2V617F more strongly than that of cells harboring WT JAK2. The 4.3-fold JAK2V617F selectivity of NS-018 is higher than the 1.0- to 2.9-fold selectivity of seven existing JAK2 inhibitors. NS-018 also inhibited erythroid colony formation in JAK2V617F transgenic mice at significantly lower concentrations than in WT mice. In keeping with the above results, in a JAK2V617F bone marrow transplantation mouse model with a myelofibrosis-like disease, NS-018 reduced leukocytosis and splenomegaly, improved bone marrow fibrosis and prolonged survival without decreasing the erythrocyte or PLT count in the peripheral blood. By exploring the X-ray co-crystal structure of NS-018 bound to JAK2, we identified unique hydrogen-bonding interactions between NS-018 and Gly993 as a plausible explanation for its JAK2V617F selectivity. These results suggest that NS-018 will have therapeutic benefit for MPN patients through both its efficacy and its reduced hematologic adverse effects.
Identifiers
What OpenQuestion holds
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.