相关实验视频

Updated: Jan 8, 2026

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis

Published on: April 5, 2017

结构导向查确定图卡替尼为MCT1/2的双重抑制剂

Binghong Xu¹, Xiaoyu Zhou², Yuanyue Shan³

¹State Key Laboratory of Synthetic Biology, Tianjin Key Laboratory of Function and Application of Biological Macromolecular Structures, School of Life Sciences, Tianjin University, Tianjin, 300072, China. binghong_xu@tju.edu.cn.

|December 11, 2025

概括

单碳酸盐转运体 (MCTs) 对癌症代谢至关重要. 这项研究揭示了图卡替尼作为MCT1和MCT2的双重抑制剂,有效地减少瘤细胞的增殖和生长,并具有良好的安全性.

科学领域:

生物化学生物化学
分子生物学分子生物学
癌症研究癌症研究

背景情况:

细胞表面葡萄糖蛋白,如embbigin,与单碳酸盐输送体 (MCTs) 形成异构体,影响它们的膜运输和功能.
癌细胞表现出代谢重编程,依赖MCT进行乳酸运输以维持糖解和维持细胞内pH值.
了解MCT调节是开发新型癌症抑制剂的关键.

研究的目的:

确定人体MCT2-embigin复合体的冷电子显微镜 (cryo-EM) 结构.
确定MCT1和MCT2载体的潜在抑制剂.
在临床前癌症模型中评估已识别的抑制剂的疗效和安全性.

主要方法:

在apo和AR-C155858结合状态下对人类MCT2-embbigin复合物的冷-EM结构确定.
基于MCT1/2结构的虚拟查以识别抑制剂.
在体外测试以评估瘤细胞增殖和迁移的抑制.
在体内研究使用老鼠异种移植模型来评估瘤生长抑制.

主要成果:

低温-EM结构显示了embbigin和MCT2之间广泛的相互作用,这对膜局部化和运输至关重要.
虚拟查发现图卡替尼是通过MCT1和MCT2.2有效抑制pyruvate运输的.
在实验室中,图卡替尼 (tucatinib) 显示出强大的宫瘤细胞增殖和迁移的抑制作用.
图卡替尼在老鼠异种移植模型中显著抑制瘤生长,具有卓越的生物安全性.

结论:

这项研究为MCT2.2的结构和功能机制提供了分子洞察力.
图卡替尼被确定为一种新的MCT1和MCT2载体的双重抑制剂.
图卡替尼 (tucatinib) 显示出作为一种潜在的治疗药物来治疗依赖于MCT介导代谢的癌症.

关键词:

宫癌宫癌是什么化电磁波是一种冷电磁波.毒品的目标是毒品的目标一氧化碳酸盐的T运输器图卡替尼布 (Tucatinib) 是一种

更多相关视频

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

相关概念视频

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...

Inhibition of Cdk Activity

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...