Advancing Target-Based Drug Design Strategy Learning in the Third-Year Pharmaceutical Science Undergraduates: Design, Synthesis and Biological Activity Evaluation of EGFR Inhibitors

Target-based drug design is a core component of the Medicinal Chemistry curriculum for pharmaceutical science undergraduate students. However, a significant gap persists between theoretical knowledge learning and experimental skill training. To fill this gap, we implemented a 6-week closed-loop experiment (4 h/per week) into the Medicinal Chemistry Experimentation course for third-year undergraduate students. This integrated module covers a target-based molecular design, retro-synthesis design, chemical synthesis, structural characterization, biological evaluation, structure–activity relationship study, and student presentations. Using epidermal growth factor receptor (EGFR) inhibitor development as a proof of concept, students complete the entire drug discovery workflow. Several strategies are employed to assess students' learning, including the prelab literature searching, in-lab practical operation and experimental observation, as well as postlab report presentation. The primary goal of this experiment is to provide students with hands-on, experiential understanding of target-based drug design. This curriculum reform not only highlights the integration theoretical knowledge of organic chemistry, spectrum elucidation, medicinal chemistry, and pharmacology into the practical training of drug discovery but also inspires the students' self-motivation in the drug development.