Exploring safe and potent bioactives for the treatment of non-small cell lung cancer.

Activating and suppressing mutations in the MAPK pathway receptors are the primary causes of NSCLC. Of note, MEK inhibition is considered a promising strategy because of the diverse structures and harmful effects of upstream receptors in MAPK pathway. Thus, we explore a total of 1574 plant-based bioactive compounds activity against MEK using an energy-based virtual screening strategy. Molecular docking, binding free energy, and drug-likeness analysis were performed through GLIDE, Prime MM-GBSA, and QikProp module, respectively. The findings indicate that 5-O-caffeoylshikimic acid has an increased binding affinity to MEK protein. Further, molecular dynamic simulations and MM-PBSA analysis were performed to explore the ligand activity in real-life situations. In essence, compounds inhibitory activity was validated across 77 lung cancer cell lines using multimodal attention-based neural network algorithm. Eventually, our analysis highlight that 5-O-caffeoylshikimic acid obtained from the bark of Rhizoma smilacis glabrae would be developed as a potential compound for treating NSCLC. © King Abdulaziz City for Science and Technology 2021.