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

Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

9.8K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
9.8K

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

Attempts to Achieve Targeted Covalent Inhibition of Hsp90β.

Chemical biology & drug design·2026
Same author

Cell-Impermeable Hsp90α-Selective Inhibitor NDNA4 Inhibits Cancer Cell Migration and Targets Extracellular Hsp90α's Critical F-5 Fragment.

ACS chemical biology·2026
Same author

Synergistic Disruption of Survival and Metastatic Potential in Esophageal Adenocarcinoma Cells Through Combined Inhibition of HIF1α and CD73.

Cancers·2025
Same author

Optimization of Hsp90/Aha1 Small-Molecule Disruptors Via the Evaluation of Amide Bioisosteres.

ACS medicinal chemistry letters·2025
Same author

Hsp90β-Selective Inhibitors: Probing the Solvent-Accessible Frontier.

ChemMedChem·2025
Same author

Integrative Multi-Omics Analyses Reveal Mechanisms of Resistance to Hsp90β-Selective Inhibition.

Cancers·2025

相关实验视频

Updated: Jun 1, 2025

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
10:58

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

17.0K

符合形态限制的Grp94-选择性抑制剂

Hao Xu1, Kyler Pugh1, Brian S J Blagg1

  • 1Department of Chemistry and Biochemistry, Warren Center for Drug Discovery, The University of Notre Dame, 305 McCourtney Hall, Notre Dame, Indiana 46556, United States.

ACS omega
|January 20, 2025
PubMed
概括

研究人员通过修改KUNG65.5开发了新的Grp94抑制剂. 化合物C6选择性地结合Grp94,显示出治疗癌症和玻璃眼等疾病的前景.

科学领域:

  • 生物化学 生物化学
  • 药用化学 医学化学
  • 分子生物学分子生物学

背景情况:

  • 葡萄糖调节蛋白94 (Grp94) 是一种独特的热冲击蛋白90 (Hsp90) 异型.
  • 选择性Grp94抑制是一种治疗初级开角玻璃眼和转移性癌症的治疗策略.

研究的目的:

  • 通过对KUNG65支架进行结构限制来设计和合成新型GRP94选择性抑制剂.
  • 为了提高 Grp94 与其他 Hsp90 异型相比的结合亲和力和选择性.

主要方法:

  • 九种KUNG65类型的符合性限制使得基分子偏向于Grp94位点1口袋.
  • 合成类似物以减少结合时的性惩罚.
  • 光极化试验以确定结合亲和力和选择性.

主要成果:

  • 化合物C6显示了Grp94的亲和力为5.52μM.
  • 化合物C6对Hsp90α没有显著的亲和力.
  • 结构约束成功地将基部分偏向到Grp94位点1口袋中.

结论:

  • 化合物C6是一种强效和选择性的Grp94抑制剂.

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
10:33

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

11.3K
Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

343

相关实验视频

Last Updated: Jun 1, 2025

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
10:58

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

17.0K
Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

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

11.3K
Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

343
  • 开发的类似物显示出对Grp94相关疾病的治疗潜力.
  • 符合性限制是设计选择性Hsp90异型抑制剂的有效策略.