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新型 CDC25 抑制剂的药物化学研究进展。

Medicinal chemistry insights into novel CDC25 inhibitors.

机构信息

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, 250012, Jinan, Shandong, PR China.

Department of Clinical Pharmacy, Qilu Hospital of Shandong University, 250012, Jinan, China.

出版信息

Eur J Med Chem. 2020 Sep 1;201:112374. doi: 10.1016/j.ejmech.2020.112374. Epub 2020 Apr 26.

Abstract

Cell division cycle 25 (CDC25) phosphatases, a kind of cell cycle regulators, have become an attractive target for drug discovery, as they have been found to be over-expressed in various human cancer cells. Several CDC25 inhibitors have achieved significant attention in clinical trials with possible mechanistic actions. Prompted by the significance of CDC25 inhibitors with medicinal chemistry prospect, it is an apt time to review the various drug discovery methods involved in CDC25 drug discovery including high throughput screening (HTS), virtual screening (VS), fragment-based drug design, substitution decorating approach, structural simplification approach and scaffold hopping method to seek trends and identify promising new avenues of CDC25 drug discovery.

摘要

细胞分裂周期蛋白 25(CDC25)磷酸酶是一种细胞周期调节剂,由于在各种人类癌细胞中过度表达,已成为药物发现的一个有吸引力的靶点。几种 CDC25 抑制剂在临床试验中引起了广泛关注,可能具有机制作用。鉴于 CDC25 抑制剂在药物化学方面的重要性和前景,现在正是回顾涉及 CDC25 药物发现的各种药物发现方法的好时机,包括高通量筛选(HTS)、虚拟筛选(VS)、基于片段的药物设计、取代修饰方法、结构简化方法和支架跳跃方法,以寻求趋势并确定有前途的 CDC25 药物发现新途径。

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