III型c-MET抑制剂(AstraZeneca)(Type-III c-MET Inhibitor(AstraZeneca)) - 药物靶点：c-Met_在研适应症：肿瘤_专利_临床

概要

基本信息

药物类型

化学药

别名-

靶点

c-Met

作用方式

抑制剂

作用机制

c-Met抑制剂(肝细胞生长因子受体抑制剂)

治疗领域

肿瘤

在研适应症

肿瘤

非在研适应症-

原研机构

AstraZeneca PLC

在研机构

AstraZeneca PLC

非在研机构-

权益机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 III型c-MET抑制剂(AstraZeneca) 相关的临床结果

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100 项与 III型c-MET抑制剂(AstraZeneca) 相关的转化医学

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100 项与 III型c-MET抑制剂(AstraZeneca) 相关的专利（医药）

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1

项与 III型c-MET抑制剂(AstraZeneca) 相关的文献（医药）

2023-07-13·Journal of medicinal chemistry1区 · 医学

Discovery and Optimization of the First ATP Competitive Type-III c-MET Inhibitor.

1区 · 医学

Article

作者: Lamb, Michelle L ; Hennessy, Edward J ; Shaw, Joseph ; Storer, R Ian ; Li, Chengzhi ; Börjesson, Ulf ; Liu, Jianming ; Cheung, Tony ; O'Neill, Daniel J ; Yang, Wenzhen ; Alkhatib, Omar ; Stubbs, Christopher J ; Wang, Peng ; Snijder, Arjan ; Qiao, Jingchuan ; Phillips, Christopher ; Wang, Jingwen ; Collie, Gavin W ; Khurana, Puneet ; Embrey, Kevin J ; Han, Fujin ; Moss, Thomas A ; Dale, Ian L ; Koh, Cheryl M ; Barlind, Louise ; Sun, Dong-Qing ; Michaelides, Iacovos N ; Vasalou, Christina

Recent clinical reports have highlighted the need for wild-type (WT) and mutant dual inhibitors of c-MET kinase for the treatment of cancer. We report herein a novel chemical series of ATP competitive type-III inhibitors of WT and D1228V mutant c-MET. Using a combination of structure-based drug design and computational analyses, ligand 2 was optimized to a highly selective chemical series with nanomolar activities in biochemical and cellular settings. Representatives of the series demonstrate excellent pharmacokinetic profiles in rat in vivo studies with promising free-brain exposures, paving the way for the design of brain permeable drugs for the treatment of c-MET driven cancers.

100 项与 III型c-MET抑制剂(AstraZeneca) 相关的药物交易

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