Discovery of novel dual-targeting inhibitors against PLK1-PBD and PLK4-PB3: structure-guided pharmacophore modelling, virtual screening, molecular docking, molecular dynamics simulation, and biological evaluation.

ABSTRACT: Aberrant expression of PLK1 and PLK4 is closely associated with tumourigenesis, and their simultaneous inhibition can effectively suppress tumour proliferation. In this study, we successfully identified peptide inhibitors (Peptides 1-5) capable of simultaneously targeting PLK1-PBD and PLK4-PB3 via pharmacophore-based virtual screening. Binding affinity analyses demonstrated that all candidate peptides exhibited nanomolar binding affinity for both targets. In vitro cancer cell growth inhibition assays revealed that these peptides could suppress the growth of cervical cancer cells. Among them, Peptide-2 showed the optimal binding affinity and anticancer cell proliferative activity (PLK1-PBD: K_d = 8.02 ± 0.16 nM; PLK4-PB3: K_d = 11.32 ± 

SUBMITTER: Zhao C 

PROVIDER: S-EPMC12265104 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature