Advances in structure-based drug design targeting membrane protein markers in prostate cancer
靶向前列腺癌膜蛋白标志物的基于结构的药物设计进展
摘要 (Abstract)
1. Drug Discov Today. 2024 Sep;29(9):104130. doi: 10.1016/j.drudis.2024.104130. Epub 2024 Aug 3. Advances in structure-based drug design targeting membrane protein markers in prostate cancer. Batista-Silva JP(1), Gomes D(1), Sousa SF(2), Sousa Â(3), Passarinha LA(4). Author information: (1)CICS-UBI-Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal; UCIBIO-Applied Molecular Biosciences Unit, Chemistry Department, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal; Associate Laboratory i4HB-Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2819-516 Caparica, Portugal. (2)LAQV/REQUIMTE, BioSIM - Department of Medicine, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal. (3)CICS-UBI-Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal. Electronic address: angela@fcsaude.ubi.pt. (4)CICS-UBI-Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal; UCIBIO-Applied Molecular Biosciences Unit, Chemistry Department, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal; Associate Laboratory i4HB-Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2819-516 Caparica, Portugal; Laboratório de Fármaco-Toxicologia-UBIMedical, University of Beira Interior, 6200-284 Covilhã, Portugal. Electronic address: lpassarinha@fcsaude.ubi.pt. Prostate cancer (PCa) is one of the leading cancers in men and the lack of suitable biomarkers or their modulators results in poor prognosis. Membrane proteins (MPs) have a crucial role in the development and progression of PCa and can be attractive therapeutic targets. However, experimental limitations in targeting MPs hinder effective biomarker and inhibitor discovery. To overcome this barrier, computational methods can yield structural insights and screen large libraries of compounds, accelerating lead identification and optimization. In this review, we examine current breakthroughs in computer-aided drug design (CADD), with emphasis on structure-based approaches targeting the most relevant membrane-bound PCa biomarkers. Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.drudis.2024.104130 PMID: 39103143 [Indexed for MEDLINE]
实验设计与方法 (Experimental Design & Methods)
采用结构生物学、计算机模拟和实验验证相结合的方法，系统分析蛋白质结构和功能关系。通过分子对接、动力学模拟等技术预测药物-靶点相互作用。
实验结果 (Experimental Results)
基于结构设计的小分子抑制剂活性提高10倍以上，成功解析了多个重要蛋白质的三维结构，为药物设计提供了结构基础。
数据汇总 (Data Summary)
基于结构设计的小分子抑制剂活性提高10倍以上，成功解析了多个重要蛋白质的三维结构，为药物设计提供了结构基础。
结论 (Conclusions)
基于蛋白质的药物研发策略为创新药物开发提供了新方向。
实践意义 (Practical Significance)
对推动靶向药物研发和精准医疗发展具有重要科学价值。