Petar Iliev, Carolin Jaworski, Carmen Wängler, Björn Wängler, Brent D G Page, Ralf Schirrmacher, Justin J Bailey
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引用次数: 0
摘要
引言Trk 家族蛋白是主要在神经元组织中表达的膜结合激酶。在神经营养素的激活下,它们通过下游信号通路调节关键的细胞过程。Trk 信号传导失调可导致一系列疾病,因此设计和研究 Trk 抑制剂是一个重要的研究领域。本综述探讨了开发 II 型和 III 型 Trk 抑制剂的最新进展,以及对各种治疗应用的影响:本综述讨论了针对Trk家族的II型和III型抑制剂的专利,作为上一篇综述《肌球蛋白受体激酶(Trk)的I型抑制剂:2020-2022年专利更新》的补充。相关专利是通过科学网数据库、谷歌和谷歌专利来确定的:虽然II型和III型Trk抑制剂的开发与I型抑制剂相比进展较为缓慢,但它们在克服耐药性突变和增强亚型选择性方面大有可为--这是减少与泛Trk抑制相关的不良反应的一个关键因素。最近的跨学科努力标志着亚型选择性 Trk 抑制剂的设计取得了重大进展,III 型抑制剂取得了令人瞩目的成功。值得注意的是,突变选择性 Trk 抑制剂的出现为这一领域引入了一个有趣的维度,提供了精确治疗的可能性。
Type II & III inhibitors of tropomyosin receptor kinase (Trk): a 2020-2022 patent update.
Introduction: The Trk family proteins are membrane-bound kinases predominantly expressed in neuronal tissues. Activated by neurotrophins, they regulate critical cellular processes through downstream signaling pathways. Dysregulation of Trk signaling can drive a range of diseases, making the design and study of Trk inhibitors a vital area of research. This review explores recent advances in the development of type II and III Trk inhibitors, with implications for various therapeutic applications.
Areas covered: Patents covering type II and III inhibitors targeting the Trk family are discussed as a complement of the previous review, Type I inhibitors of tropomyosin receptor kinase (Trk): a 2020-2022 patent update. Relevant patents were identified using the Web of Science database, Google, and Google Patents.
Expert opinion: While type II and III Trk inhibitor development has advanced more gradually compared to their type I counterparts, they hold significant promise in overcoming resistance mutations and achieving enhanced subtype selectivity - a critical factor in reducing adverse effects associated with pan-Trk inhibition. Recent interdisciplinary endeavors have marked substantial progress in the design of subtype selective Trk inhibitors, with impressive success heralded by the type III inhibitors. Notably, the emergence of mutant-selective Trk inhibitors introduces an intriguing dimension to the field, offering precise treatment possibilities.
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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