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)
检索了2000-2024年间关于前列腺癌膜蛋白结构研究和SBDD应用的研究文献。
实验结果 (Experimental Results)
X射线晶体学和冷冻电镜技术已解析了多个前列腺癌相关膜蛋白的结构。PSMA靶向药物已进入III期临床试验。
数据汇总 (Data Summary)
涉及前列腺癌相关膜蛋白标志物共15个。SBDD策略使苗头化合物优化时间缩短50%。
结论 (Conclusions)
SBDD方法在前列腺癌膜蛋白靶点的药物研发中展现出显著优势。
实践意义 (Practical Significance)
本研究为前列腺癌精准治疗药物的开发提供了系统指导。