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The Cysteinome of Protein Kinases as a Target in Drug Development
Angewandte Chemie International Edition ( IF 16.6 ) Pub Date : 2018-02-02 , DOI: 10.1002/anie.201707875
Apirat Chaikuad 1, 2 , Pierre Koch 3 , Stefan A. Laufer 3, 4 , Stefan Knapp 1, 2, 5, 6
Affiliation  

Drugs that function through covalent bond formation represent a considerable fraction of our repository of effective medicines but safety concerns and the complexity of developing covalent inhibitors has rendered covalent targeting a less attractive strategy for rational drug design. The recent approval of four covalent kinase inhibitors and the development of highly potent covalent kinase probes with exceptional selectivity has raised significant interest in industry and academic research and validated the concept of covalent kinase targeting for clinical applications. The abundance of cysteines at diverse positions in and around the kinase active site suggests that a large fraction of kinases can be targeted by covalent inhibitors. Herein, we review recent developments of this rapidly growing area in kinase drug development and highlight the unique opportunities and challenges of this strategy.

中文翻译:

半胱氨酸蛋白激酶作为药物开发的目标。

通过共价键形成起作用的药物占我们有效药物库的很大一部分,但是安全性问题和开发共价抑制剂的复杂性使得以共价键为目标的合理药物设计策略不那么吸引人。四种共价激酶抑制剂的最新批准以及具有非凡选择性的高效共价激酶探针的开发引起了业界和学术研究的极大兴趣,并验证了针对临床应用的共价激酶靶向的概念。在激酶活性位点内和周围不同位置的半胱氨酸丰富表明,共价抑制剂可靶向大部分激酶。在此处,
更新日期:2018-02-02
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