三阴性乳腺癌（TNBC）是一种侵袭性恶性肿瘤，需要有效的靶向药物治疗。本研究采用计算机辅助方法评估了七种已批准使用的药物对人ck2α激酶的疗效，该激酶是TNBC转移和侵袭的重要调控因子。分子对接结果显示，共结晶参考抑制剂108600的对接得分为（-7.390 kcal/mol）。值得注意的是，在测试的七种已批准使用的药物中，舒尼替尼，巴泽多辛和依托韦他它们的对接得分优于参考抑制剂。具体而言，它们的对接得分分别为-10.401，-7.937和-7.743 kcal/mol。进一步的MM/GBSA分析表明，这三种排名靠前的药物比参考配体具有更好的结合能。随后的分子动力学模拟确定了依托韦他，一种经FDA批准的抗病毒药物，作为唯一的再利用药物，它在各种分析指标，包括RMSD，RMSF和旋转半径等方面与人类ck2α蛋白表现出稳定可靠的结合模式。主成分分析表明，依托韦他与人类ck2α蛋白的复合物具有与共结晶抑制剂相似的运动稳定性。此外，对依托韦他与一个代表性金原子在依托韦他的异原子相对位置上形成的复合物进行了密度泛函理论（DFT）计算。DFT计算结果显示出低能量的复合物，可能作为金纳米载体的依托韦他的实验试验指南，增强其对恶性细胞的输送，并引入一条新的药物输送途径。基于本研究获得的结果，依托韦他显示出作为靶向TNBC的潜在抗肿瘤药物的潜力，值得通过实验和临床评估进一步的研究。版权：© 2023 Shoaib et al。本文是以知识共享署名许可协议发布的开放获取文章，在任何媒介下都可以自由使用、分发和重制，只要原始作者和来源被署名。

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 of TNBC metastasis and invasiveness. Molecular docking revealed that the co-crystallized reference inhibitor 108600 achieved a docking score of (-7.390 kcal/mol). Notably, among the seven approved drugs tested, sunitinib, bazedoxifene, and etravirine exhibited superior docking scores compared to the reference inhibitor. Specifically, their respective docking scores were -10.401, -7.937, and -7.743 kcal/mol. Further analysis using MM/GBSA demonstrated that these three top-ranked drugs possessed better binding energies than the reference ligand. Subsequent molecular dynamics simulations identified etravirine, an FDA-approved antiviral drug, as the only repurposed drug that demonstrated a stable and reliable binding mode with the human ck2 alpha protein, based on various analysis measures including RMSD, RMSF, and radius of gyration. Principal component analysis indicated that etravirine exhibited comparable stability of motion as a complex with human ck2 alpha protein, similar to the co-crystallized inhibitor. Additionally, Density functional theory (DFT) calculations were performed on a complex of etravirine and a representative gold atom positioned at different sites relative to the heteroatoms of etravirine. The results of the DFT calculations revealed low-energy complexes that could potentially serve as guides for experimental trials involving gold nanocarriers of etravirine, enhancing its delivery to malignant cells and introducing a new drug delivery route. Based on the results obtained in this research study, etravirine shows promise as a potential antitumor agent targeting TNBC, warranting further investigation through experimental and clinical assessments.Copyright: © 2023 Shoaib et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.