Crystal Structures of Neurotrophin Receptors Kinase Domain

被引:4
作者
Bertrand, T. [1 ]
机构
[1] Sanofi, Vitry Sur Seine, France
来源
NEUROTROPHINS | 2017年 / 104卷
关键词
NERVE GROWTH-FACTOR; IMMUNOGLOBULIN-LIKE DOMAINS; TYROSINE PROTEIN-KINASE; BINDING DOMAIN; TRKA RECEPTOR; INHIBITORS; CANCER; SPECIFICITY; EXPRESSION; INSIGHTS;
D O I
10.1016/bs.vh.2016.10.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Neurotrophins and their receptors (Trk) play key roles in the development of the nervous system and in cell survival. Trk receptors are therefore attractive pharmacological targets for brain disorders as well as for cancers. While the druggability of the extracellular domain of the receptors, that specifically binds neurotrophins, is yet to be proven, the intracellular kinase domains are attractive targets for small-molecule binding. The recent crystal structures of the three isoforms of the Trk family, TrkA, TrkB, and TrkC have been described in their apo forms and in complex with potent and selective pan-Trk inhibitors. The description of the kinase domain of each of the isoforms will be discussed in their apo forms or bound to potent inhibitors of interest in cancer therapy. Non-oncology indications and selectivity issues will also be discussed.
引用
收藏
页码:1 / 18
页数:18
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