Jove
Visualize
联系我们
JoVE
x logofacebook logolinkedin logoyoutube logo
关于 JoVE
概览领导团队博客JoVE 帮助中心
作者
出版流程编辑委员会范围与政策同行评审常见问题投稿
图书馆员
用户评价订阅访问资源图书馆顾问委员会常见问题
研究
JoVE JournalMethods CollectionsJoVE Encyclopedia of Experiments存档
教育
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab Manual教师资源中心教师网站
使用条款与条件
隐私政策
政策

相关概念视频

Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

5.2K
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
5.2K

您也可能阅读

相关文章

通过共同作者、期刊和引用图与本文相关的文章。

排序
Same author

Targeting the TBK1-p62 condensate axis restores sensitivity to EGFR-TKIs in resistant lung cancer.

Protein & cell·2026
Same author

Aurora-A drives sorafenib resistance by scaffolding stress granule assembly via phase separation.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same author

CDK1-mediated phosphorylation of LDHA fuels mitosis through LDHB-dependent lactate oxidation.

EMBO reports·2025
Same author

Comprehensive profiling of the catalytic conformations of human Guanylate kinase.

Nature communications·2025
Same author

piRNA gene density and SUMOylation organize piRNA transcriptional condensate formation.

Nature structural & molecular biology·2025
Same author

Repurposing Tolfenamic Acid to Anchor the Uncharacterized Pocket of the PUB Domain for Proteolysis of the Atypical E3 Ligase HOIP.

ACS chemical biology·2024

相关实验视频

Updated: Jan 15, 2026

A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4
06:56

A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4

Published on: March 10, 2018

14.4K

基于碎片发现的小分子RhoGDI2连接体,HR3119,抑制癌细胞迁移.

Mingqing Liu1, Shizhang Wan2, Shuangxi Guo2

  • 1The First Affiliated Hospital and School of Life Sciences, Ministry of Education Key Laboratory for Membrane-less Organelles and Cellular Dynamics, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, Biomedical Sciences and Health Laboratory of Anhui Province, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, China.

ACS chemical biology
|October 16, 2025
PubMed
概括

研究人员发现了HR3119,这是第一个针对RhoGDI2的小分子,RhoGDI2是一种参与癌症的蛋白质. 这种化合物破坏了RhoGDI2-Rac1结合,并抑制了侵袭性乳腺癌细胞迁移,为新药发现提供了前景.

更多相关视频

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

9.4K
Characterization of the Effects of Migrastatic Inhibitors on 3D Tumor Spheroid Invasion by High-resolution Confocal Microscopy
09:17

Characterization of the Effects of Migrastatic Inhibitors on 3D Tumor Spheroid Invasion by High-resolution Confocal Microscopy

Published on: September 16, 2019

7.2K

相关实验视频

Last Updated: Jan 15, 2026

A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4
06:56

A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4

Published on: March 10, 2018

14.4K
A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
07:41

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

Published on: February 20, 2018

9.4K
Characterization of the Effects of Migrastatic Inhibitors on 3D Tumor Spheroid Invasion by High-resolution Confocal Microscopy
09:17

Characterization of the Effects of Migrastatic Inhibitors on 3D Tumor Spheroid Invasion by High-resolution Confocal Microscopy

Published on: September 16, 2019

7.2K

科学领域:

  • 生物化学 生物化学
  • 分子生物学分子生物学
  • 药物发现 药物发现 药物发现

背景情况:

  • 关氨酸核酸解离抑制剂 (GDI),如RhoGDI2,调节Ras超级家族蛋白质,这些蛋白质是癌症药物的关键标.
  • 直接准Ras蛋白具有挑战性,使RhoGDI2等GDI成为癌症治疗的有吸引力的替代标.
  • 以前针对GDI的努力取得了有限的成功,突出了对新方法的需求.

研究的目的:

  • 为发现和描述RhoGDI2.2的第一个小分子连接体.
  • 研究小分子可以破坏RhoGDI2-蛋白相互作用的机制.
  • 在侵袭性乳腺癌模型中评估RhoGDI2抑制剂的治疗潜力.

主要方法:

  • 采用基于碎片的药物发现方法,从一个毫米相亲度的命中开始.
  • 基于结构的药物设计,以联体结合的RhoGDI2的晶体结构为指导,用于优化化合物.
  • 生物化学测试用于确定结合亲和力 (Kd) 并评估蛋白质-蛋白质相互作用的破坏.
  • 基于细胞的测试被用来评估该化合物对癌细胞迁移的影响.

主要成果:

  • HR3119被确定为第一个具有低微分子亲和度 (Kd = 8 μM) 的RhoGDI2配体.
  • HR3119被理性地设计为占据RhoGDI2-Rac1蛋白质-蛋白质相互作用接口,有效地破坏它们的结合.
  • HR3119 的 (6R) - 反体与 (6S) - 反体相比,显示出明显更高的结合亲和力 (近100倍).
  • (6R) -HR3119在细胞中激活了RhoGDI2,并抑制了侵袭性乳腺癌细胞的迁移.

结论:

  • HR3119代表了一种新的,第一类的小分子,针对RhoGDI2.
  • 这项研究表明,通过基于结构的设计来发现RhoGDI2抑制剂的成功策略.
  • 针对RhoGDI2的化合物,如 (6R) -HR3119显示希望开发新的治疗方法来对抗侵袭性乳腺癌.