相关实验视频

Updated: Jun 1, 2025

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

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

实验,理论和在中研究潜在的CDC7激酶抑制剂

Kannika Byadarahalli Ravindranath¹, Saravanan Kandasamy², Hossam Ebaid³

¹Department of Pharmaceutical Biosciences, Uppsala University, Husargatan 3, Uppsala 752 37, Sweden.

|January 20, 2025

概括

合成和表征了两种新的pyrazole衍生物. 计算研究显示,与CDC7-激酶有很强的结合 afinities,这表明潜在的治疗应用.

科学领域:

药用化学医学化学
计算化学的计算化学
晶体学晶体学是指结晶学.

背景情况:

皮拉衍生物已知具有多种生物活性.
了解分子相互作用对于药物设计至关重要.

研究的目的:

为了合成和描述两个pyrazole衍生物.
研究它们的晶体结构和分子间相互作用.
通过in silico研究来评估它们作为CDC7-激酶抑制剂的潜力.

主要方法:

单晶X射线衍射用于固态特性.
希尔什菲尔德表面分析和分子中的原子量子理论 (QTAIM) 用于分子间相互作用.
密度函数理论 (DFT) 用于结构优化.
分子对接和动力学模拟用于与CDC7-酶结合的亲和力.

主要成果:

化合物I和II以C-H·O键结晶为单临床系统.
希尔什菲尔德分析表明,H···H相互作用在晶体包装中占主导地位.
DFT优化的结构与实验数据密切匹配.
这两种化合物都显示出与CDC7-激酶具有显著的结合自由能量,主要是通过范德瓦尔斯力.

结论:

合成的皮拉衍生物表现出明确的晶体结构和分子间相互作用.
在 silico 研究证实了它们作为 CDC7-kinase 的有效配体的潜力.
这些发现支持进一步研究这些化合物用于治疗开发.

更多相关视频

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

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

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

Published on: January 22, 2019

相关概念视频

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...

M-Cdk Drives Transition Into Mitosis

M-Cdk Drives Transition Into Mitosis

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...