*3.8. Molecular Docking Study*

The ligand structures (**10**, **11**, and Ravoxertinib) were prepared using ChemDraw Ultra 15.0 (Perkin Elmer, MA, USA). The protonation state of **10** and **11** were prepared using Open Babel GUI and Command Prompt with pH 7.4. To predict the potential binding interactions between the compounds and the core targets, an in silico assay was conducted using PyRx Virtual Screening Tools v0.8. The X-ray crystal structures of the proteins were obtained from the Protein Data Bank (https://www.rcsb.org/, accessed on 16 March 2023), e.g., 6GES for MAPK3 (ERK1) and 1WZY for MAPK1 (ERK2). Prior to the analysis, the proteins were prepared by removing water molecules and any other ligands attached to the main protein using Pymol v2.5 (https://pymol.org/2/, accessed on 16 March 2023). The free binding energies (ΔG), interaction types, and amino acid residues were calculated and analyzed using BIOVIA Discovery Studio Visualizer 2022 (Biovia, CA, USA).
