Pengyun Li, Bingkun Li, Ning Yang, Tingting Xu, Zhibing Zheng
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引用次数: 0
摘要
简介:表皮生长因子受体(EGFR)的异常表达有助于肿瘤的发展,尤其是在癌症(NSCLC)中。尽管已经开发出多种抑制剂来靶向不同的EGFR突变,并且有几种已经获得批准,但不可避免的耐药性和副作用仍然是一个挑战,这激发了新的策略。蛋白质水解靶向嵌合体(PROTACs)通过触发蛋白质降解,作为人类疾病的新疗法,其潜力越来越大。到目前为止,已经发现了各种强效和特异性EGFR PROTAC,其中一些已经进入临床试验。涵盖领域:本综述概述了2016年至2022年专利中的EGFR降解剂。它提供了所有可用EGFR PROTAC的发现策略、化学结构和分子图谱的更新。SciFinder、PubMed、Web of Science、EPO和CNIPA数据库用于搜索EGFR PROTAC的文献和专利。专家意见:通过采用PROTAC技术,已经开发出基于四代EGFR抑制剂的高效选择性EGFR降解剂,为靶向EGFR突变和克服耐药性提供了一种新的策略。尽管在体外和体内研究中取得了令人满意的结果,但它们的治疗价值仍有待更严格的临床前测试和临床研究。
The next generation of EGFR inhibitors: a patenting perspective of PROTACs based EGFR degraders.
Introduction: Abnormal expression of epidermal growth factor receptor (EGFR) contributes to tumor development, especially in non-small cell lung cancer (NSCLC). Although multiple inhibitors have been developed to target diverse EGFR mutations and several have been approved, the inevitable drug resistance and side effect remain a challenge, which motivates novel strategies. Proteolysis-targeting chimeras (PROTACs) have been gaining momentum for their potential as novel therapeutics for human diseases by triggering protein degradation. To date, various potent and specific EGFR PROTACs have been discovered and some of them have entered clinical trials.
Areas covered: This review provides an overview of EGFR degraders in patents from 2016 to 2022. It provides an update of the discovery strategies, chemical structures, and molecular profiling of all available EGFR PROTACs. SciFinder, PubMed, Web of Science, EPO, and CNIPA databases were used for searching the literature and patents for EGFR PROTACs.
Expert opinion: By employing the PROTAC technology, highly potent and selective EGFR degraders based on four generation EGFR inhibitors have been developed, which offer a new strategy to target EGFR mutations and overcome the drug resistance. Despite the satisfactory result in vitro and in vivo studies, their therapeutic value awaits more rigorous preclinical testing and clinical investigation.
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
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