Identification of potential casein kinase I isoform epsilon inhibitors from phytoconstituents: implications for targeted anticancer therapeutics

Casein kinase I isoform epsilon (CK1ε) demonstrates significant implications in cancer pathogenesis, influencing key cellular processes linked to oncogenesis. Its regulatory roles in cell survival, proliferation, and modulation of oncogenic pathways highlight CK1ε as a potential target for therapeutic strategies in diverse cancer types. In this research, a virtual screening of phytoconstituents from the IMPPAT2.0 database was conducted to find potential inhibitors targeting CK1ε. Initially, compounds adhering to Lipinski’s rule of five were retrieved, followed by filtering based on binding affinities and subsequent interaction analyses to refine the selection. Finally, two compounds, Chrysin-7-O-Glucuronide and Rhodiolin, demonstrated considerable affinities with specific interactions at the CK1ε ATP binding site (involving SER17, SER19, and LYS38), forming hydrogen bonds, and were identified for further analysis <i>via</i> PASS server. Employing all-atom molecular dynamic (MD) simulations for 200 ns, structural deviation, residual fluctuation, compactness by radius of gyration, solvent accessible surface area calculation, principal component analysis, and free energy landscapes, were conducted. These findings suggest that Chrysin-7-O-Glucuronide and Rhodiolin warrant further investigation in experimental and clinical research as potential candidates for developing anticancer therapeutics targeting CK1ε kinase.