Discovery of Palbociclib as a potent c-Myc G4 stabilizer for lung cancer treatment using molecular docking, molecular dynamics simulation, and in vitro activity evaluation.

Despite significant progress in lung cancer treatment, this disease remains a prevalent and serious global malignancy, leading to high rates of illness and death. Urgent research is needed to discover new or alternative therapies that can improve clinical outcomes for lung cancer patients. In our study, we successfully demonstrated the effectiveness of Palbociclib, a CDK4/6 inhibitor, in suppressing the growth of lung cancer cells. The IC 50 values obtained were 11.00 μM and 11.74 μM for H1299 and A549 cells, respectively. Furthermore, our findings indicate that Palbociclib may possess strong c-Myc G4 stabilizing properties by significantly reducing both protein and mRNA expression levels of c-Myc. Additionally, Palbociclib induces apoptosis and causes cell cycle arrest at the G2/M phase in two cells. Through circular dichroism (CD), molecular docking, and molecular dynamics (MD) simulation, we have provided evidence that Palbociclib enhances the structural stability of c-Myc G4 while exhibiting a high binding affinity to its ligand's binding site on c-Myc G4. These results suggest that Palbociclib holds promise as a novel c-Myc G4 stabilizer for treating cancers associated with abnormal c-Myc activity; further optimization and development are warranted.