Related Experiment Video
Updated: Jul 12, 2026
Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
Published on: August 12, 2015
Binding investigation of Ribociclib to human α-1-acid glycoprotein with spectroscopic and computational simulation
Liang Han1, Yan-Fei Jin1, Li Li2
1College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, China.
Abstract:
Ribociclib, a selective small-molecule CDK4/6 inhibitor, was approved by the US FDA in 2017. It is administered in combination with endocrine therapy to treat advanced or metastatic HR+/HER2-breast cancer in premenopausal, perimenopausal, and postmenopausal women. The interaction of Ribociclib with human α-1-acid glycoprotein (HAG) was investigated through multi-spectroscopic techniques and molecular simulation approaches to elucidate its pharmacokinetic and pharmacodynamic properties. The results show that Ribociclib binds to HAG and forms a 1:1 complex, leading to the fluorescence quenching of HAG. Van der Waals forces, hydrogen bonds, and hydrophobic interactions dominate the binding of Ribociclib to HAG, as indicated by thermodynamic data and competition experiments. This conclusion is further corroborated by molecular docking simulations. The binding of Ribociclib induces a subtle conformational change in HAG, as revealed by molecular dynamics simulation and circular dichroism (CD) measurements. The observed redshift in the 3D fluorescence spectra suggests increased hydrophilicity of the microenvironment around the HAG binding sites. In addition, several common metal ions reduce the affinity of Ribociclib to HAG, as shown by a decrease in the binding constants. These findings provide valuable insight into Ribociclib's mechanism of action and could guide future structural optimization to enhance its therapeutic profile.
Insights
Ribociclib binds to human α-1-acid glycoprotein (HAG) forming a 1:1 complex, primarily through van der Waals forces, hydrogen bonds, and hydrophobic interactions. This interaction influences Ribociclib
Area of Science:
- Pharmacology and Biochemistry
- Molecular Interactions
- Drug Discovery
Background:
- Ribociclib is an FDA-approved CDK4/6 inhibitor for HR+/HER2- advanced breast cancer.
- Understanding drug-protein interactions is crucial for optimizing pharmacokinetic and pharmacodynamic properties.
Purpose of the Study:
- To investigate the binding interaction between Ribociclib and human α-1-acid glycoprotein (HAG).
- To elucidate the molecular mechanisms governing this interaction and its impact on Ribociclib's properties.
Main Methods:
- Multi-spectroscopic techniques (fluorescence quenching, 3D fluorescence spectra).
- Molecular simulation approaches (molecular docking, molecular dynamics).
- Circular dichroism (CD) measurements and thermodynamic analysis.
Main Results:
- Ribociclib forms a 1:1 complex with HAG, causing fluorescence quenching.
- Binding is driven by van der Waals forces, hydrogen bonds, and hydrophobic interactions.
- Ribociclib binding induces subtle conformational changes in HAG, increasing local hydrophilicity.
Conclusions:
- The study elucidates the molecular basis of Ribociclib-HAG interaction.
- Findings offer insights into Ribociclib's pharmacokinetics and pharmacodynamics.
- Results may guide future structural modifications for enhanced therapeutic efficacy.
More Related Videos
10:24NMR-Based Activity Assays for Determining Compound Inhibition, IC50 Values, Artifactual Activity, and Whole-Cell Activity of Nucleoside Ribohydrolases
Published on: June 30, 2019
14:34A Bilingual Computational Workflow for Identifying Potential PLK1 Inhibitors in American Sign Language and English
Published on: April 3, 2026
