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c-Met 激酶抑制剂:专利更新综述(2014-2017)。

c-Met kinase inhibitors: an update patent review (2014-2017).

机构信息

a Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry , China Pharmaceutical University , Nanjing , P. R. China.

出版信息

Expert Opin Ther Pat. 2019 Jan;29(1):25-41. doi: 10.1080/13543776.2019.1552261. Epub 2018 Dec 12.

Abstract

INTRODUCTION

The receptor tyrosine kinase c-Met is involved in the formation, metastasis and invasion of various malignant tumors thus it has been an attractive target for anti-tumor drug designing. Many compositions targeting c-Met have been developed in pharmaceutical industry for cancer therapy and some of them are in clinical study now. Among them, Crizotinib was the first small molecular inhibitor approved by FDA in 2011.

AREAS COVERED

This review briefly summarizes the signal transduction pathway about c-Met, its role in oncogenesis, most recent patents of small-molecule inhibitors and antibodies of c-Met from 2014 to 2017.

EXPERT OPINION

To date, some c-Met inhibitors have been launched in the market. In addition, their clinical performances have shown encouraging value in cancer therapy. Many potential agents are still in preclinical or clinical study now and achieve some promising progressions. Some patients have developed resistance to c-Met inhibitors which results in the need to develop inhibitors with novel structures. Development of several potent drugs also tends to be pharmacodynamically active against multiple targets.

摘要

简介

受体酪氨酸激酶 c-Met 参与多种恶性肿瘤的形成、转移和侵袭,因此它一直是抗肿瘤药物设计的一个有吸引力的靶点。制药行业已经开发出许多针对 c-Met 的药物成分,用于癌症治疗,其中一些目前正在临床研究中。其中,克唑替尼是 2011 年 FDA 批准的第一个小分子抑制剂。

涵盖领域

本文简要总结了 c-Met 的信号转导通路及其在肿瘤发生中的作用,以及 2014 年至 2017 年 c-Met 的小分子抑制剂和抗体的最新专利。

专家意见

迄今为止,一些 c-Met 抑制剂已经上市。此外,它们在癌症治疗中的临床表现显示出令人鼓舞的价值。许多潜在的药物仍处于临床前或临床研究阶段,并取得了一些有希望的进展。一些患者对 c-Met 抑制剂产生了耐药性,这就需要开发具有新型结构的抑制剂。几种有效药物的开发也倾向于对多个靶点具有药效活性。

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