Progress with polo-like kinase (PLK) inhibitors: a patent review (2018-present).

IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Expert Opinion on Therapeutic Patents Pub Date : 2024-09-01 Epub Date: 2024-07-15 DOI:10.1080/13543776.2024.2379924
Shirong Bian, Ru Zhang, Jianyu Nie, Mingxing Zhu, Zhouling Xie, Chenzhong Liao, Qin Wang
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Abstract

Introduction: Polo-like kinases (PLKs) have five isoforms, all of which play crucial roles in cell cycle and cell proliferation, offering opportunities for drug design and treatment of cancers and other related diseases. Notably, PLK1 and PLK4 have been extensively investigated as cancer drug targets. One distinctive feature of PLKs is the presence of a unique polo-box domain (PBD), which regulates kinase activity and subcellular localization. This provides possibilities for specifically targeting PLKs.

Area covered: This article provides an overview of the roles of PLKs in various cancers and related diseases, as well as the drug development involving PLKs, with a particular focus on PLK1 and PLK4. It summarizes the PLK1 and PLK4 inhibitors that have been disclosed in patents or literature (from 2018 - present), which were sourced from SciFinder and WIPO database.

Expert opinion: After two decades of drug development on PLKs, several drugs progressed into clinical trials for the treatment of many cancers; however, none of them has been approved yet. Further elucidating the mechanisms of PLKs and identifying and developing highly selective ATP-competitive inhibitors, highly potent drug-like PBD inhibitors, degraders, etc. may provide new opportunities for cancer therapy and the treatment for several nononcologic diseases. PLKs inhibition-based combination therapies can be another helpful strategy.

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多聚样激酶(PLK)抑制剂的进展:专利回顾(2018年至今)。
导言:Polo-like激酶(PLKs)有五种同工酶,它们都在细胞周期和细胞增殖中发挥关键作用,为癌症和其他相关疾病的药物设计和治疗提供了机会。值得注意的是,PLK1 和 PLK4 已作为癌症药物靶点被广泛研究。PLK 的一个显著特点是存在一个独特的多聚酶盒结构域 (PBD),该结构域可调节激酶活性和亚细胞定位。这为特异性靶向 PLKs 提供了可能性:本文概述了 PLKs 在各种癌症和相关疾病中的作用,以及涉及 PLKs 的药物开发,尤其关注 PLK1 和 PLK4。文章总结了已在专利或文献中公开的 PLK1 和 PLK4 抑制剂(从 2018 年至今),这些专利或文献均来自 SciFinder 和 WIPO 数据库:经过二十年的PLKs药物研发,一些药物已进入临床试验阶段,用于治疗多种癌症,但目前还没有一种药物获得批准。进一步阐明PLKs的作用机制,鉴定和开发高选择性ATP竞争性抑制剂、强效类药物PBD抑制剂、降解剂等,可为癌症治疗和多种非肿瘤性疾病的治疗提供新的机遇。以 PLKs 抑制剂为基础的联合疗法可能是另一种有用的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
12.10
自引率
1.50%
发文量
50
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Therapeutic Patents (ISSN 1354-3776 [print], 1744-7674 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on recent pharmaceutical patent claims, providing expert opinion the scope for future development, in the context of the scientific literature. The Editors welcome: Reviews covering recent patent claims on compounds or applications with therapeutic potential, including biotherapeutics and small-molecule agents with specific molecular targets; and patenting trends in a particular therapeutic area Patent Evaluations examining the aims and chemical and biological claims of individual patents Perspectives on issues relating to intellectual property The audience consists of scientists, managers and decision-makers in the pharmaceutical industry and others closely involved in R&D Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days.
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