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基于计算机的端粒酶抑制剂设计。

In silico design of telomerase inhibitors.

机构信息

Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, 80-233 Gdansk, Poland.

Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, 80-233 Gdansk, Poland.

出版信息

Drug Discov Today. 2020 Jul;25(7):1213-1222. doi: 10.1016/j.drudis.2020.04.024. Epub 2020 May 6.

Abstract

Telomerase is a reverse transcriptase enzyme involved in DNA synthesis at the end of linear chromosomes. Unlike in most other cells, telomerase is reactivated most cancerous cells and, therefore, has become a promising new anticancer target. Despite extensive research, direct telomerase inhibitors have yet not been introduced to the clinics because of the complexity of this enzyme. Structures of this protein from simple organisms and human homology models are currently available and have been used in structure-based drug design efforts to find potential inhibitors. Different is silico strategies have been applied and different chemical groups have been explored. Here, we provide an overview of recent discoveries.

摘要

端粒酶是一种逆转录酶,参与线性染色体末端的 DNA 合成。与大多数其他细胞不同,端粒酶在大多数癌细胞中被重新激活,因此已成为一种有前途的新的抗癌靶点。尽管进行了广泛的研究,但由于该酶的复杂性,直接的端粒酶抑制剂尚未被引入临床。目前已有来自简单生物体的这种蛋白质的结构和人类同源模型,并已用于基于结构的药物设计工作,以寻找潜在的抑制剂。已经应用了不同的计算机策略,并探索了不同的化学基团。在这里,我们提供了最近发现的概述。

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