相关实验视频

Updated: Jan 8, 2026

In Vitro Imaging and Quantification of the Drug Targeting Efficiency of Fluorescently Labeled GnRH Analogues

In Vitro Imaging and Quantification of the Drug Targeting Efficiency of Fluorescently Labeled GnRH Analogues

Published on: March 21, 2017

合成和优化LHQ766:一种高度选择性的FGFR2抑制剂,具有改善的药理动力学

Huiqiong Li¹, Qiuju Xun¹, Bowen Yang¹

¹State Key Laboratory of Chemical Biology and Shanghai Hongkong Joint Laboratory in Chemical Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, #345 Lingling Rd., Shanghai, 200032, China.

European journal of medicinal chemistry

|December 19, 2025

概括

一种新药物LHQ766显示出作为一种口服可用的纤维细胞生长因子受体2 (FGFR2) 抑制剂的强大潜力,用于癌症治疗. 它显示出高强度,选择性和针对性治疗的改善药理动力学特性.

科学领域:

在瘤学瘤学.
药用化学医学化学
药理学药理学是指药理学的学科.

背景情况:

纤维细胞生长因子受体2 (FGFR2) 是癌症治疗中的关键治疗标.
以前的FGFR2抑制剂显示出有希望的结果,但需要优化.

研究的目的:

开发和描述LHQ766,一种新的,口服生物可用,强大的FGFR2抑制剂.
评估LHQ766在向癌症治疗中的疗效和药理动力学特性.

主要方法:

使用NMR,HRMS和HPLC进行结构确认.
酶和细胞测试以确定IC50值.
计算建模和质谱仪用于机械学研究.
在老鼠中进行的药理动力学研究.

主要成果:

LHQ766证明了强大的酶抑制 (IC50 = 7.3 nM) 和细胞活性 (IC50 = 0.5 nM) 对FGFR2.2.
该化合物表现出高激酶选择性,节省了FGFR1/3/4和72种其他激酶.
机理学研究揭示了与FGFR2.2的共价结合模式.
在FGFR2驱动的癌症模型中,LHQ766显示了剂量依赖的途径抑制和抗增殖效应.
在大鼠中,获得了最佳的口服生物利用率 (35.9%).

结论:

LHQ766是一种高度强效和选择性的FGFR2抑制剂,具有良好的口服生物可用性.
该化合物有效地准FGFR2信号通路,并表现出抗增殖作用.
在瘤学中,LHQ766代表了开发向FGFR2治疗的有希望的领先候选人.

关键词:

防止核武器的扩散.协同抑制剂协同抑制剂在FGFR2中.口服生物可用性口服生物可用性选择性的选择性

更多相关视频

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells

Published on: April 9, 2018

相关概念视频

Drug Discovery: Overview

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...

Structure-Activity Relationships and Drug Design

Structure-Activity Relationships and Drug Design

Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...