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Rethinking JAK2 inhibition: towards novel strategies of more specific and versatile janus kinase inhibition

Leukemia volume 31, pages 1023–1038 (2017)Cite this article

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A Corrigendum to this article was published on 06 December 2017

Abstract

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. On the basis of 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.

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Acknowledgements

We thank Drs Andrew K. Shiau, Leila Varghese and Thomas Radimerski for critical comments. We acknowledge FRIA PhD and Salus Sanguinis fellowships to EL. Support to SNC was from Ludwig Institute for Cancer Research, the Fondation contre le cancer (Grant Number F/2004/266), from Actions de Recherche Concertées of the communauté Française de Belgique (Grant Number ARC10/15-027) and the PAI program Belgian Medical Genetics Initiative (Grant Number IAP-P7/43).

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  1. Christian de Duve Institute, Ludwig Institute for Cancer Research and Université catholique de Louvain, de Duve Institute, Brussels, Belgium

    E Leroy & S N Constantinescu

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  1. E Leroy
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Correspondence to S N Constantinescu.

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Leroy, E., Constantinescu, S. Rethinking JAK2 inhibition: towards novel strategies of more specific and versatile janus kinase inhibition. Leukemia 31, 1023–1038 (2017). https://doi.org/10.1038/leu.2017.43

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  • DOI: https://doi.org/10.1038/leu.2017.43

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