Discovery of natural scaffolds as HER2 inhibitors for breast cancer: virtual screening, molecular dynamics, and biological characterization with selectivity profiling.

ABSTRACT: Nature offers potential therapeutic candidates for breast cancer (BC), and targeting HER2 signaling presents a promising approach, leveraging the successful history of anticancer drug discovery. Using a structure-based virtual screening workflow, a comprehensive library of natural products (NPs) was screened for potential HER2 binding. Five of these NPs were selected for in-depth biological validation against BC. Biochemically, oroxin B, liquiritin, ligustroflavone, and mulberroside A suppressed HER2 catalysis with nanomolar potency. Binding mode studies of NPs revealed their binding patterns, providing valuable SAR insights for effective HER2 inhibition. Further cellular assays revealed that the top NPs have preferential anti-proliferative effects towards HER2 over-expressing BC cells, wi

SUBMITTER: Hossam A 

PROVIDER: S-EPMC12267471 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature