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丝裂原活化蛋白激酶(MAPK)抑制剂的专利综述(2018年至今)。

A patent review of MAPK inhibitors (2018 - present).

作者信息

Wydra Valentin R, Ditzinger Raphael B, Seidler Nico J, Hacker Frederik W, Laufer Stefan A

机构信息

Department of Pharmaceutical and Medicinal Chemistry, Eberhard Karls Universit't Tübingen, Tübingen, Germany.

Cluster of Excellence iFIT (EXC2180) "Image-Guided & Functionally Instructed Tumor Therapies", Eberhard Karls Universität Tübingen, Tübingen, Germany.

出版信息

Expert Opin Ther Pat. 2023 Jan-Jun;33(6):421-444. doi: 10.1080/13543776.2023.2242584. Epub 2023 Aug 1.

DOI:10.1080/13543776.2023.2242584
PMID:37501497
Abstract

INTRODUCTION

The mitogen-activated protein kinase (MAPK) family consist of p38 MAP kinases, c-Jun N-terminal kinases (JNKs) and extracellular signal-regulated kinases (ERKs). They are involved in a multitude of diseases, including inflammatory, autoimmune, neurodegenerative, and metabolic diseases as well as cancer. In recent years, further developments in the field of MAPK-inhibitors have been reported, including an isoform or downstream target selective inhibition of MAPKs as well as target protein degradation approaches.

AREAS COVERED

This review summarizes newly patented MAPK-inhibitors that were claimed between 2018 and early 2023. Presented are the patents as well as their corresponding publications, the storyline of development, and clinical trials involving these compounds. This article elaborates a total of 27 patents, which were identified using established search engines.

EXPERT OPINION

Although industrial research on MAPK-inhibitors has been ongoing for more than 20 years, novel clinical trials of MAPK-inhibitors as potential drug candidates are still being conducted in the period under review. Recently reported inhibitors show an excellent selectivity profile and are even achieving selectivity between closely related isoforms. This progression offers the possibility to eliminate unwanted side effects and may finally lead to the approval of the first MAPK-inhibitor.

摘要

引言

丝裂原活化蛋白激酶(MAPK)家族由p38 MAP激酶、c-Jun氨基末端激酶(JNK)和细胞外信号调节激酶(ERK)组成。它们参与多种疾病,包括炎症性、自身免疫性、神经退行性和代谢性疾病以及癌症。近年来,有报道称MAPK抑制剂领域有进一步的进展,包括对MAPK的亚型或下游靶点的选择性抑制以及靶向蛋白降解方法。

涵盖领域

本综述总结了2018年至2023年初获得专利的新型MAPK抑制剂。介绍了这些专利及其相应的出版物、研发历程以及涉及这些化合物的临床试验。本文共阐述了27项专利,这些专利是使用成熟的搜索引擎识别出来的。

专家观点

尽管对MAPK抑制剂的工业研究已经进行了20多年,但在本审查期间仍在进行将MAPK抑制剂作为潜在候选药物的新型临床试验。最近报道的抑制剂显示出优异的选择性,甚至在密切相关的亚型之间实现了选择性。这一进展提供了消除不良副作用的可能性,并最终可能导致首个MAPK抑制剂获得批准。

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