The human kinome and kinase inhibition.
The human kinome and kinase inhibition.
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DOI：
10.1002/0471141755.ph0209s60
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发表时间：
2013-03
影响因子：
--
通讯作者：
Peterson, Jeffrey R
中科院分区：
文献类型：
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作者：
Duong-Ly, Krisna C;Peterson, Jeffrey R
蛋白质和脂质激酶在许多生物过程中发挥着关键的调节作用。毫不奇怪，激酶的激活突变与许多紊乱和疾病有关，尤其是癌症。因此，激酶已成为有前景的临床靶标。人类有超过500种蛋白激酶和大约20种脂质激酶。大多数蛋白激酶共享一个高度保守的结构域，即真核蛋白激酶 (ePK) 结构域，其中包含 ATP 和底物结合位点。临床使用的许多抑制剂与高度保守的 ATP 结合位点结合。因此，许多激酶抑制剂并不是专门针对其预期靶点的选择性。此外，尽管目前人们对激酶抑制剂很感兴趣，但与疾病有关的激酶很少有经过验证的抑制剂。本单元描述了人类激酶组、ePK 结构和激酶抑制剂的类型，重点关注鉴定有效和选择性激酶抑制剂的方法。协议。药理学。 60：2.9.1‐2.9.14。 © 2013 John Wiley & Sons, Inc. 版权所有
Protein and lipid kinases play key regulatory roles in a number of biological processes. Unsurprisingly, activating mutations in kinases have been linked to a number of disorders and diseases, most notably cancers. Thus, kinases have emerged as promising clinical targets. There are more than 500 human protein kinases and about 20 lipid kinases. Most protein kinases share a highly conserved domain, the eukaryotic protein kinase (ePK) domain, which contains the ATP and substrate‐binding sites. Many inhibitors in clinical use bind to the highly conserved ATP binding site. For this reason, many kinase inhibitors are not exclusively selective for their intended targets. Furthermore, despite the current interest in kinase inhibitors, very few kinases implicated in disease have validated inhibitors. This unit describes the human kinome, ePK structure, and types of kinase inhibitors, focusing on methods to identify potent and selective kinase inhibitors.Curr. Protoc. Pharmacol. 60:2.9.1‐2.9.14. © 2013 by John Wiley & Sons, Inc.