激酶变构抑制剂: 一种新的高效和高选择性调节激酶活性的方式

doi:10.5246/jcps.2012.06.068

摘要/Abstract

摘要：

研究证明, 激酶活性失控是导致癌症的原因之一, 癌细胞存活和增殖与相应激酶活性的失控密切相关。选择性的抑制激酶活性已经成为开发安全有效的抗癌药的重点研究领域。到目前为止, 已有15种激酶抑制剂得到美国食品药品监督管理局的批准用于治疗多种癌症。其中, 激酶的变构抑制剂在临床上显示出更好的安全性和有效性。本文将总结这些激酶的变构构象、它们对应的抑制剂及其作用方式。

关键词: 蛋白激酶, 变构构象, DFG-out, ATP非竞争性, 激酶抑制剂

Abstract:

Dysregulation of kinases has been proven to be one of the main causes of abnormal growth and survival of cancer cells. Selective modulations of kinase activities have become the focus of many research programs for the development of safe and effective chemotherapy for cancers. So far, fifteen kinase inhibitors have received FDA approval for the treatment of various forms of cancers. Among them, the allosteric kinase inhibitors have been shown to have superior clinical profile in terms of safety and efficacy. In this review, we summarize the allosteric conformations of kinases, their corresponding inhibitors and the modes of their interactions.

Key words: Protein kinase, Allosteric conformation, DFG-out, ATP non-competitive, Kinase inhibitor

中图分类号:

R962.1

Supporting:

^*Corresponding author. Tel.: 86-431-85619260

杨洪亮, 陈婷, 柏旭, 裴亚中^*. 激酶变构抑制剂: 一种新的高效和高选择性调节激酶活性的方式[J]. , DOI: 10.5246/jcps.2012.06.068.

Hongliang Yang, Ting Chen, Xu Bai, Yazhong Pei^* . Allosteric kinase inhibitors: a new paradigm for effective and selective modulation of kinase activities [J]. , DOI: 10.5246/jcps.2012.06.068.

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