Targeting the Non-Catalytic Functions: a New Paradigm for Kinase Drug Discovery?
Targeting the Non-Catalytic Functions: a New Paradigm for Kinase Drug Discovery?
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针对非催化功能：激酶药物发现的新范式？
DOI：
10.1021/acs.jmedchem.1c01978
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发表时间：
2022-01-09
影响因子：
7.3
通讯作者：
Ding, Ke
中科院分区：
文献类型：
--
作者：
Wang, Zhen;Huang, Weixue;Ding, Ke
在过去的二十年中，蛋白激酶已经成为癌症药物发现的非常富有成效的靶标，而这些药物中的大多数结合到“三磷酸腺苷（ATP）位点”并抑制激酶催化活性。近年来，越来越多的证据表明，激酶通过其支架具有催化作用以外的功能，并且支架功能在多种细胞信号传导和细胞命运控制中发挥着重要作用。小分子调节激酶的非催化功能的报道很少，但出现了各种疾病的新的有前途的治疗策略。本文综述了激酶的非催化功能，并重点介绍了激酶非催化功能小分子调节剂的研究进展。还讨论了不同类型调节剂的作用机制和特点。它也被推测，针对非催化功能将代表一个新的方向激酶为基础的药物发现。
Protein kinases have been highly fruitful targets for cancer drug discovery in the past two decades, while most of these drugs bind to the "adenosine triphosphate (ATP)-site" and inhibit kinase catalytic activity. Recently, accumulated evidence suggests that kinases possess functions beyond catalysis through their scaffolds, and the scaffolding functions could play critical roles in multiple cellular signaling and cell fate controls. Small molecules modulating the noncatalytic functions of kinases are rarely reported but emerge as new promising therapeutic strategies for various diseases. Herein, we summarize the characterized noncatalytic functions of kinases, and highlight the recent progress on developing small-molecule modulators of the noncatalytic functions of kinases. Mechanisms and characteristics of different kinds of modulators are also discussed. It is also speculated that targeting the noncatalytic functions would represent a new direction for kinase-based drug discovery.
影响因子：
3.1
作者：
Marlowe, Timothy;Alvarado, Carlos;Rivera, Andrew;Lenzo, Felicia;Nott, Rohini;Bondugji, Dena;Montoya, Justin;Hurley, Alana;Kaplan, Matt;Capaldi, Andrew;Cance, William
通讯作者：
Cance, William