Exploring the potential of approved drugs for triple-negative breast cancer treatment by targeting casein kinase 2: Insights from computational studies

• DOI: 10.1371/journal.pone.0289887
• Publication Date: 2023-08-14T17:24:53Z
• Authors: Tagyedeen H. Shoaib; Walaa Ibraheem; Mohammed Abdelrahman; Wadah Osman; Asmaa E. Sherif; Ahmed Ashour; Sabrin R. M. Ibrahim; Kholoud F. Ghazawi; Samar F. Miski; Sara A. Almadani; Duaa Fahad ALsiyud; Gamal A. Mohamed; Abdulrahim A. Alzain
• Keywords: Etravirine; Triple-negative breast cancer; AutoDock; Docking (animal)

Triple-negative breast cancer (TNBC) is an aggressive malignancy that requires effective targeted drug therapy. In this study, we employed in silico methods to evaluate the efficacy of seven approved drugs against human ck2 alpha kinase, a significant modulator TNBC metastasis and invasiveness. Molecular docking revealed co-crystallized reference inhibitor 108600 achieved score (-7.390 kcal/mol). Notably, among tested, sunitinib, bazedoxifene, etravirine exhibited superior scores compared inhibitor. Specifically, their respective were -10.401, -7.937, -7.743 kcal/mol. Further analysis using MM/GBSA demonstrated these three top-ranked possessed better binding energies than ligand. Subsequent molecular dynamics simulations identified etravirine, FDA-approved antiviral drug, as only repurposed stable reliable mode with protein, based on various measures including RMSD, RMSF, radius gyration. Principal component indicated comparable stability motion complex similar Additionally, Density functional theory (DFT) calculations performed representative gold atom positioned at different sites relative heteroatoms etravirine. The results DFT low-energy complexes could potentially serve guides for experimental trials involving nanocarriers enhancing its delivery malignant cells introducing new route. Based obtained research shows promise potential antitumor agent targeting TNBC, warranting further investigation through clinical assessments.