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小分子激酶抑制剂治疗非肿瘤疾病。

Small-Molecule Kinase Inhibitors for the Treatment of Nononcologic Diseases.

机构信息

Department of Pharmaceutical Sciences and Engineering, School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China.

出版信息

J Med Chem. 2021 Feb 11;64(3):1283-1345. doi: 10.1021/acs.jmedchem.0c01511. Epub 2021 Jan 22.

Abstract

Great successes have been achieved in developing small-molecule kinase inhibitors as anticancer therapeutic agents. However, kinase deregulation plays essential roles not only in cancer but also in almost all major disease areas. Accumulating evidence has revealed that kinases are promising drug targets for different diseases, including cancer, autoimmune diseases, inflammatory diseases, cardiovascular diseases, central nervous system disorders, viral infections, and malaria. Indeed, the first small-molecule kinase inhibitor for treatment of a nononcologic disease was approved in 2011 by the U.S. FDA. To date, 10 such inhibitors have been approved, and more are in clinical trials for applications other than cancer. This Perspective discusses a number of kinases and their small-molecule inhibitors for the treatment of diseases in nononcologic therapeutic fields. The opportunities and challenges in developing such inhibitors are also highlighted.

摘要

在开发小分子激酶抑制剂作为抗癌治疗药物方面已经取得了巨大的成功。然而,激酶失调不仅在癌症中而且在几乎所有主要疾病领域都起着至关重要的作用。越来越多的证据表明,激酶是治疗包括癌症、自身免疫性疾病、炎症性疾病、心血管疾病、中枢神经系统疾病、病毒感染和疟疾在内的不同疾病的有前途的药物靶点。事实上,美国 FDA 于 2011 年批准了第一个用于治疗非肿瘤疾病的小分子激酶抑制剂。迄今为止,已有 10 种此类抑制剂获得批准,更多的抑制剂正在临床试验中用于癌症以外的应用。本观点讨论了一些激酶及其小分子抑制剂在非肿瘤治疗领域治疗疾病的情况。还强调了开发此类抑制剂的机遇和挑战。

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