Repurposing risperidone as an anti-angiogenic agent for triple-negative breast cancer: a computational to

Introduction: Triple-negative breast cancer (TNBC) is a challenging subtype of breast cancer to treat because it lacks the expression of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER2). A significant majority of deaths related to cancer are caused by tumor metastasis and angiogenesis. Vascular endothelial growth factor receptor 2 (VEGFR2) plays a significant role in angiogenesis. Instead of developing new molecules, drug repurposing, also known as repositioning, seeks innovative uses for outdated drugs or those that fail due to ineffectiveness. Methods: In this study, we performed high-throughput virtual screening of FDA approved drug library taken from Enamine bioactive collection targeting VEGFR proteins, and the top hit compounds analyzed by molecular dynamics simulations and MM-GBSA were considered for further Results: The results revealed that risperidone was effective against triple-negative breast cancer, with IC50 values ranging from 46.53 to 49.76 µM. The findings of our study demonstrated that risperidone, an antipsychotic drug, could successfully inhibit human breast cancer cells in silico, Discussion: We could prove that a structure-based drug repurposing approach is an effective strategy to produce a promising antiangiogenic repurposed drug that could also inhibit VEGFR2 in breast cancer. Although risperidone showed modest potency, its clinical availability and repurposing potential support further evaluation in preclinical and clinical settings.