SHP2异构抑制剂专利回顾(2018年至今)。

IF 5.4 2区 医学 Q1 CHEMISTRY, MEDICINAL Expert Opinion on Therapeutic Patents Pub Date : 2024-05-01 Epub Date: 2024-06-13 DOI:10.1080/13543776.2024.2365410
Alessia Petrocchi, Alina Ciammaichella
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引用次数: 0

摘要

导言:SHP2(含Src同源区2的蛋白酪氨酸磷酸酶2)在受体酪氨酸激酶(RTK)下游的RAS/MAPK信号转导通路的调控中起着关键作用,因此是癌症治疗的一个受关注的靶点。此外,SHP2 还能通过 PD-1/PD-L1 通路抑制 T 细胞。SHP2 在细胞增殖、存活和迁移等众多生理和病理过程中发挥着关键作用:本综述研究了 2018 年至今在 Espacenet 和 Scifinder 数据库中公布的专利中报告的 SHP2 异生抑制剂。综述了权利要求结构,重点关注与SHP099(首个描述的SHP2异构抑制剂)相比的结构修饰:多种强效的SHP2异构抑制剂已被发现、公开,并在多种临床前癌症模型中进行了测试,其疗效证据确凿。目前有 15 种化合物处于临床开发阶段,但没有一种获准上市。迄今为止,由于获得性耐药机制和/或缺乏疗效,SHP2 抑制剂作为单一疗法药物的长期益处尚未得到证实。不过,与 MEK、BRAF、表皮生长因子受体、RAS-G12C 和 PDL-1 抑制剂等多种药物的联合疗法潜力巨大,目前是一个广泛的研究领域。
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A patent review of SHP2 allosteric inhibitors (2018-present).

Introduction: SHP2 (Src homology region 2-containing protein tyrosine phosphatase 2) is a target of interest for cancer therapy due to its key role in the regulation of the RAS/MAPK signal transduction pathway downstream of Receptor Tyrosine Kinases (RTKs). Moreover, SHP2 can inhibit T cells via the PD-1/PD-L1 pathway. SHP2 plays a critical role in numerous physiological and pathological cellular processes, such as cell proliferation, survival, and migration.

Areas covered: This review examines SHP2 allosteric inhibitors reported in patents published in Espacenet and Scifinder databases from 2018 to present. An overview of claimed structures is conducted, focusing attention on structural modifications compared to SHP099, the first described allosteric inhibitor of SHP2.

Expert opinion: Multiple potent allosteric SHP2 inhibitors have been discovered, disclosed, and tested in a variety of preclinical cancer models with strong evidence of efficacy. Fifteen compounds are currently in clinical development, but none of them have been approved for marketing. Until now, long-term benefit of SHP2 inhibitors as monotherapy agents have not been demonstrated due to acquired mechanisms of resistance and/or lack of efficacy. However, combination therapies with a variety of agents, such as MEK, BRAF, EGFR, RAS-G12C and PDL-1 inhibitors, have high potential and are currently an extensive area of investigation.

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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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