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

被引：59

作者：

Leroy, E.

Constantinescu, S. N. ^{[1
,2
]}

机构：

[1] Ludwig Inst Canc Res, Christian de Duve Inst, Ave Hippocrate 74, B-1200 Brussels, Belgium

[2] Catholic Univ Louvain, de Duve Inst, Ave Hippocrate 74, B-1200 Brussels, Belgium

来源：

LEUKEMIA | 2017年 / 31卷 / 05期

关键词：

THROMBOPOIETIN RECEPTOR ACTIVATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; SMALL-MOLECULE INHIBITOR; PSEUDOKINASE-DOMAIN; TYROSINE KINASE; CYTOKINE-RECEPTOR; MYELOPROLIFERATIVE NEOPLASMS; PROTEIN-KINASE; PHASE-I; SIGNAL-TRANSDUCTION;

D O I：

10.1038/leu.2017.43

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1023 / 1038

页数：16

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