在可逆共价激酶抑制剂的进展
Zheng Zhao1,2, Philip E Bourne1,2
1School of Data Science, University of Virginia, Charlottesville, Virginia, USA.
Medicinal research reviews
|September 17, 2024
概括
可逆共价激酶抑制剂 (RCKI) 提供有针对性的选择性,而不会永久损害蛋白质. 本综述详细介绍了RCKI的设计策略,并推进了它们对酶和非酶标的开发.
科学领域:
- 药用化学 医学化学
- 药理学 药理学是指药理学的学科.
- 药物发现 药物发现 药物发现
背景情况:
- 可逆共价激酶抑制剂 (RCKI) 正成为一个有前途的治疗策略.
- 它们结合了共价抑制剂的选择性,降低了永久性不良反应的风险.
- 目前正在研究RCKIs的各种激酶,包括非典型组,其中一些候选人在临床试验中.
研究的目的:
- 系统地审查可逆共价激酶抑制剂 (RCKI) 的进展.
- 总结关键特征,包括电友性群,化学支架,核友性残留物和结合方式.
- 提供对有效设计策略和RCKI发展的未来前景的见解.
主要方法:
- 对RCKIs的系统文献综述.
- 对电友性群体,化学支架和核友性残留物的分析.
- 检查绑定模式和结构-活动关系.
主要成果:
- RCKIs表现出一系列的电友群和化学支架.
- 了解核性残留物分布对于有效的RCKI设计至关重要.
- 已经确定了特权电友和特定的结合模式.
结论:
- RCKIs代表了激酶抑制剂开发的重大进步.
- 有效的设计策略利用了对电友和核友的见解.
- 未来的研究方向包括将RCKI应用扩展到酶之外.
更多相关视频
11:11Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach
Published on: February 21, 2019
7.4K
10:33Development 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
相关概念视频
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
M-Cdk Drives Transition Into Mitosis
5.5K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.5K
Targeted Cancer Therapies
7.5K
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...
There are several types of targeted therapies against...
7.5K
Conservative Site-specific Recombination and Phase Variation
5.9K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
5.9K
