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Rethinking JAK2 Inhibition: Towards Novel Strategies of More Specific and Versatile Janus Kinase Inhibition

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Leroy, Emilie [UCL] Constantinescu, Stefan N. [UCL]

Janus kinases (JAKs) are required for cytokine receptor signaling. Since the discovery of the highly prevalent JAK2 V617F mutation in myeloproliferative neoplasms (MPNs), JAK2 became a prime target for inhibition. Only one approved JAK2 inhibitor exists, with positive, but not curative effects in MPNs, and promising effects in autoimmune diseases and cancer. Based on recent advances in the structural features regulating both normal and mutant JAKs, as well as in small-molecule targeting, we review the current state of JAK2 inhibitor development and present novel avenues of selecting JAK2 inhibitors, with broad and narrow specificities and extend these approaches to other JAKs.

Document type Article de périodique (Journal article) – Synthèse de littérature
Access type Accès libre
Publication date 2017
Language Anglais
Journal information "Leukemia" - Vol. 31, no. 5, p. 1023-1038 (2017)
Peer reviewed yes
Publisher Nature Publishing Group ((United Kingdom) London)
issn 0887-6924
e-issn 1476-5551
Publication status Publié
Affiliations UCL - SSS/DDUV - Institut de Duve
UCL - SSS/DDUV/SIGN - Cell signalling
UCL - (SLuc) Service d'hématologie
Links
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Bibliographic reference Leroy, Emilie ; Constantinescu, Stefan N.. Rethinking JAK2 Inhibition: Towards Novel Strategies of More Specific and Versatile Janus Kinase Inhibition. In: Leukemia, Vol. 31, no. 5, p. 1023-1038 (2017)
Permanent URL http://hdl.handle.net/2078.1/181521