JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders

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JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders

JAK inhibitors have been developed following the discovery of the JAK2V617F in 2005 as the driver mutation of the majority of non- BCR-ABL1 myeloproliferative neoplasms (MPNs). Subsequently, the search for JAK2 inhibitors continued with the discovery that the other driver mutations ( CALR and MPL) also exhibited persistent JAK2 activation. Several type I ATP-competitive JAK inhibitors with diff...

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JAK inhibitors in myeloproliferative neoplasms

27 Introduction The Janus kinases (JAKs) are a family of 4 nonreceptor tyrosine kinases that play an essential role in mediating cytokine signalling. JAKs associate with cytokine receptors that lack intrinsic kinase activity to mediate cytokine-induced signal transduction via the activation of the STAT transcription factors and other signalling pathways (Figure 1, page 28).1,2 The 4 family memb...

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JAK inhibitors for myeloproliferative neoplasms: clarifying facts from myths.

On November 16, 2011, the Food and Drug Administration approved ruxolitinib (a JAK1 and JAK2 inhibitor) for use in the treatment of high and intermediate risk myelofibrosis. This is welcome news for those patients in whom such therapy is indicated and treatment benefit outweighs attendant risk. The question is who are these patients, what should they expect in terms of both short-term effects a...

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Perspectives JAK inhibitors for myeloproliferative neoplasms: clarifying facts from myths

On November 16, 2011, the Food and Drug Administration approved ruxolitinib (a JAK1 and JAK2 inhibitor) for use in the treatment of high and intermediate risk myelofibrosis. This is welcome news for those patients in whom such therapy is indicated and treatment benefit outweighs attendant risk. The question is who are these patients, what should they expect in terms of both short-term effects a...

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Combination treatment for myeloproliferative neoplasms using JAK and pan-class I PI3K inhibitors

Current JAK2 inhibitors used for myeloproliferative neoplasms (MPN) treatment are not specific enough to selectively suppress aberrant JAK2 signalling and preserve physiological JAK2 signalling. We tested whether combining a JAK2 inhibitor with a series of serine threonine kinase inhibitors, targeting nine signalling pathways and already used in clinical trials, synergized in inhibiting growth ...

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ژورنال

عنوان ژورنال: F1000Research

سال: 2018

ISSN: 2046-1402

DOI: 10.12688/f1000research.13167.1