Bioinfo Chem
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Volume 7 Number 1 2025
RESEARCH ARTICLE (Open Access)
Virtual Screening and Computational Analysis of Natural Compound Targeting CDK4/6 for Pan-Cancer Therapeutic Potential
Shahadat Hossain1*, Farhana Ferdushi Aion2, Badhan Mojumder2
Bioinfo Chem 7 (1) 1-8 https://doi.org/10.25163/bioinformatics.7110529
Submitted: 05 July 2025 Revised: 18 September 2025 Accepted: 23 September 2025 Published: 25 September 2025
Abstract
Background: The CDK4 and CDK6 regulate the transition from G1 phase to the S phase in the cell cycle. Overexpression of CDK4, or CDK6 leads to uncontrolled proliferation and is seen in many cancers. Palbociclib is effective but limited through toxicity and resistance developed to it. Besides, very few comparative studies have evaluated natural compound Luteolin against CDK4/6. Consequently, the study intends to assess the inhibitory potential, binding affinity, and structural stability of Luteolin and Palbociclib through molecular docking and computational interactions studies.
Methods: This study used an in silico comparative study of Luteolin and Palbociclib. The 3D structures of CDK4 (2W9Z) and CDK6 (2EUF) were obtained using PyMOL followed by docking using PyRx. Analysis of protein target classification, pathway enrichment, and interaction networks were carried out using Swiss Target Prediction, ShinyGO, and STRING database. Graph Pad Prism was used to analyze and visualize of the docking scores and RMSD stability profiles.
Results: The docking outcomes revealed that the binding affinities of Luteolin with CDK6 (-9.7 kcal/mol) and CDK4 (-8.7 kcal/mol) was high. The compound was found to target several receptors, enzymes and kinases. This shows that the pathways PI3K-AKT, MAPK and hormones were heavily involved According to RMSD profiling, the Luteolin-bound complexes were more stable than Palbociclib.
Conclusion: Luteolin appears a low-toxicity, multi-target CDK4/6 inhibitor with therapeutic potential across cancers. Because it can hit different signaling pathways at the same time, the drug can overcome limitations of palbociclib type drugs.
Keywords: CDK4/6 Inhibition, Luteolin, Molecular Docking, Palbociclib, Cell Cycle Regulation
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