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通过计算药物重新定位、药物基因组学、分子对接和分子动力学模拟研究，从美国食品药品监督管理局（FDA）批准的药物中探索潜在的尤因肉瘤药物。

Exploration of Potential Ewing Sarcoma Drugs from FDA-Approved Pharmaceuticals through Computational Drug Repositioning, Pharmacogenomics, Molecular Docking, and MD Simulation Studies.

作者信息

Hassan Mubashir, Yasir Muhammad, Shahzadi Saba, Kloczkowski Andrzej

机构信息

Institute of Molecular Biology and Biotechnology, The University of Lahore, Defense Road Campus, Lahore 54590, Pakistan.

The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio 43205, United States.

出版信息

ACS Omega. 2022 Jun 1;7(23):19243-19260. doi: 10.1021/acsomega.2c00518. eCollection 2022 Jun 14.

DOI:10.1021/acsomega.2c00518
PMID:35721972
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9202290/
Abstract

Novel drug development is a time-consuming process with relatively high debilitating costs. To overcome this problem, computational drug repositioning approaches are being used to predict the possible therapeutic scaffolds against different diseases. In the current study, computational drug repositioning approaches were employed to fetch the promising drugs from the pool of FDA-approved drugs against Ewing sarcoma. The binding interaction patterns and conformational behaviors of screened drugs within the active region of Ewing sarcoma protein (EWS) were confirmed through molecular docking profiles. Furthermore, pharmacogenomics analysis was employed to check the possible associations of selected drugs with Ewing sarcoma genes. Moreover, the stability behavior of selected docked complexes (drugs-EWS) was checked by molecular dynamics simulations. Taken together, astemizole, sulfinpyrazone, and pranlukast exhibited a result comparable to pazopanib and can be used as a possible therapeutic agent in the treatment of Ewing sarcoma.

摘要

新型药物研发是一个耗时的过程，成本高昂且令人疲惫。为克服这一问题，计算药物重新定位方法正被用于预测针对不同疾病的可能治疗支架。在当前研究中，采用计算药物重新定位方法从美国食品药品监督管理局（FDA）批准的药物库中获取针对尤因肉瘤的有前景药物。通过分子对接图谱确认了筛选出的药物在尤因肉瘤蛋白（EWS）活性区域内的结合相互作用模式和构象行为。此外，采用药物基因组学分析来检查所选药物与尤因肉瘤基因的可能关联。此外，通过分子动力学模拟检查所选对接复合物（药物 - EWS）的稳定性行为。综上所述，阿司咪唑、磺吡酮和普仑司特表现出与帕唑帕尼相当的结果，可作为治疗尤因肉瘤的可能治疗药物。

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