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

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

4.7K
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...
4.7K

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

Structure and mechanism of inhibition of lysine demethylase 2A (KDM2A) by compound 183c.

Communications chemistry·2026
Same author

Structural Transformation of a BRAF Inhibitor into a Selective PKR Inhibitor.

Journal of medicinal chemistry·2026
Same author

Accuracy and homogeneity of dictionary-based T2-mapping dedicated to single slice and multi-slice multi-echo turbo-spin echo imaging.

Magnetic resonance imaging·2026
Same author

The PLK4 inhibitor RP-1664 demonstrates potent efficacy in neuroblastoma preclinical models through a dual mechanism of sensitivity.

Nature communications·2026
Same author

Dual-Species Fermentation of a <i>Lycium barbarum</i>-<i>Polygonatum cyrtonema</i> Composite Jiaosu Enhanced Antioxidant Activity and Alleviated Alcohol-Induced Liver Injury in Mice.

Foods (Basel, Switzerland)·2026
Same author

The molecular glue CLEO4-88 inhibits the ACAA1 thiolase by induced binding to GID4.

Nature chemical biology·2026

相关实验视频

Updated: Jun 15, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.1K

发现RP-1664:一类中的第一口服生物可用,选择性PLK4抑制剂.

Frédéric Vallée1, Matias Casás-Selves1, Monica Bubenik1

  • 1Repare Therapeutics, Inc., 7210 Frederick-Banting, Ville St-Laurent, QC H4S 2A1, Canada.

Journal of medicinal chemistry
|May 16, 2025
PubMed
概括

研究人员开发了RP-1664,一种强大的Polo类激酶4 (PLK4) 抑制剂,用于使用TRIM37基因放大来治疗癌症. 这种候选药物显示了改善的特性,现在正在第一阶段的临床试验中.

更多相关视频

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
12:40

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

Published on: December 7, 2014

14.9K
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

17.9K

相关实验视频

Last Updated: Jun 15, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.1K
A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
12:40

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

Published on: December 7, 2014

14.9K
Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

17.9K

科学领域:

  • 在瘤学瘤学.
  • 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:

  • 波罗样类激酶4 (PLK4) 对于中心球生物生成至关重要,并且在癌症中通过TRIM37基因放大具有合成致命性.
  • 以前的PLK4抑制剂在选择性和药理动力学特性方面面临着挑战.
  • 已知抑制剂Centrinone B表现出代谢不稳定性和口服生物可用性较差.

研究的目的:

  • 开发一种具有强大和选择性的PLK4抑制剂,具有改进的类似药物的特性.
  • 确定用于TRIM37增强癌症的新型治疗剂.

主要方法:

  • 基于结构的药物设计 (SBDD) 用于优化Centrinone B.
  • 进行了基因组分析,以评估对相关基因酶的选择性.
  • 临床前研究评估了RP-1664在异种移植模型中的药理动力学,药理动力学和疗效.

主要成果:

  • 与之前的抑制剂相比,RP-1664显示出强度,选择性和ADME特性显著改善.
  • 在AURKA/B和PLK1基因酶上观察到精致的选择性.
  • RP-1664有效地扰乱了中心生物发生,在体内显示了目标参与,并在TRIM37增强异种移植模型中证明了有效性.

结论:

  • RP-1664 是一流的临床候选者,针对PLK4用于TRIM37增强癌症.
  • 优化的抑制剂表现出有利的药理动力学和强大的抗瘤活性.
  • 目前RP-1664正在进行高级固体瘤的第一阶段临床试验.