Background:Breast cancer is a frequently diagnosed malignant disease and the primary
cause of mortality among women with cancer worldwide. The therapy options are influenced by the
molecular subtype due to the intricate nature of the condition, which consists of various subtypes.
By focusing on the activation of receptors, Epidermal Growth Factor Receptor (EGFR) tyrosine kinase
can be utilized as an effective drug target for therapeutic purposes of breast cancer.Objectives:The objective of this study is to compare the underlying pharmacological properties of
several modified agents to the parental Cordycepin to target and inhibit the EGFR tyrosine kinase
high expression, and to discover the inhibitor with the highest affinity for this drug target to treat the
breast cancer patients.Methods:The Maestro Application of Schrödinger Suite Paid Software was initially employed for
conducting extra precision (XP) structure-based virtual screening to evaluate the binding affinity of
the Cordycepin and its 500 structural derivatives with the EGFR tyrosine kinase protein structure. In
addition, the anti-breast cancer activity of the chosen compounds was assessed by looking at their
drug-likeness and ADMET characteristics using Lipinski's rule of five along with Quantitative structure-
activity relationship (QSAR) validation, the prediction of cell line anti-cancer, as well as anti-
breast cancer activity of top docked scored compounds. Subsequently, the Desmond paid software-
based molecular dynamics simulations (MDS) were conducted for a duration of 100 nanoseconds
on the promising candidates followed by the binding free energy estimation was performed
utilizing MM-GBSA analysis. To determine the stability of the protein-ligand complex, root-meansquare
deviation (RMSD), root-mean-square fluctuation (RMSF), protein-ligand interactions, and
other necessary parameters were evaluated from the 100 ns MDS Trajectory.Results:Based on the overall analysis of our study, N (6)-octylamine adenosine (CID-194932) reported
the optimum inhibitory potential against the EGFR tyrosine kinase protein, followed by
Adenosine 5-monophosphate (CID-83862) and Cordycepin (CID-6303), which compared favorably
to the control drug Vandetanib (CID-3081361).Conclusion:Consequently, these derivative compounds Cordycepin have the potential
to be utilized as lead molecules in the development of highly effective and potent EGFR
tyrosine kinase inhibitors for the treatment of breast cancer patients.