Design and Discovery of Silmitasertib-based Drugs as a Potential Casein Kinase II Inhibitor for Cholangiocarcinoma through Hybrid In-silico Ligand-Based Virtual Screening with Molecular Docking Method

Abstract

This research investigates the design and discovery of silmitasertib-based drugs as potential inhibitors of casein kinase II (CK2) for cholangiocarcinoma using hybrid in-silico methods. The study employs a two-fold approach, including ligand-based virtual screening and molecular docking, to assess the inhibitory potential of silmitasertib-based compounds. The ligand-based virtual screening involves the construction of a diverse compound library, followed by energy minimization and conformational analysis, revealing a set of compounds with varied similarities to silmitasertib. In parallel, the CK2 model undergoes meticulous selection, validation, and refinement through PDB REDO, showcasing significant improvements in model quality. Molecular docking results highlight promising candidates, with N-(2, 4, 6-trimethylphenyl) phenanthridin-6-amine (MCULE-1492185963-0) emerging as a lead compound with superior binding characteristics compared to silmitasertib. This hybrid in-silico approach demonstrates the potential of silmitasertib-based compounds as CK2 inhibitors for cholangiocarcinoma and identifies a lead compound for further experimental validation. The findings contribute valuable insights to the design of novel drugs for cholangiocarcinoma treatment, setting the stage for future experimental and clinical investigations