Multidimensional insights into squalene epoxidase drug development: in vitro mechanisms, in silico modeling, and in vivo implications.

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Ahmed A Allam, Hassan A Rudayni, Noha A Ahmed, Faris F Aba Alkhayl, Al Mokhtar Lamsabhi, Emadeldin M Kamel
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引用次数: 0

Abstract

Introduction: Squalene epoxidase (SQLE) is a pivotal enzyme in sterol biosynthesis, catalyzing the conversion of squalene to 2,3-oxidosqualene. Beyond its core role in cholesterol homeostasis, SQLE is implicated in cancer, hypercholesterolemia, and fungal infections, positioning it as a valuable therapeutic target.

Areas covered: We conducted a comprehensive literature search across primary databases to gather in vitro, in silico, and in vivo evidence on SQLE. This review explores the enzyme's structural and functional features, including substrate specificity and catalytic mechanisms, and examines inhibitor interactions. Computational methods predict enzyme - inhibitor dynamics, guiding drug design, while in vivo investigations clarify SQLE's role in metabolic disorders and tumorigenesis. Challenges include drug resistance and study discrepancies, but emerging technologies, such as cryo-electron microscopy and CRISPR editing, offer new avenues for deeper exploration.

Expert opinion: SQLE is an underexplored yet promising therapeutic target, with particular relevance to oxidative stress, ferroptosis, and gut microbiota research. Overcoming current barriers through advanced technologies and multidisciplinary strategies could propel SQLE-targeted treatments into clinical practice, supporting precision medicine and broader translational applications.

多维洞察角鲨烯环氧化酶药物开发:体外机制,在硅模型,和体内的影响。
简介:角鲨烯环氧化酶(SQLE)是甾醇生物合成中的关键酶,可催化角鲨烯转化为2,3-氧化角鲨烯。除了其在胆固醇稳态中的核心作用外,SQLE还与癌症、高胆固醇血症和真菌感染有关,使其成为一个有价值的治疗靶点。涵盖领域:我们在主要数据库中进行了全面的文献检索,以收集SQLE的体外、计算机和体内证据。这篇综述探讨了酶的结构和功能特征,包括底物特异性和催化机制,并研究了抑制剂的相互作用。计算方法预测酶抑制剂动力学,指导药物设计,而体内研究阐明SQLE在代谢紊乱和肿瘤发生中的作用。挑战包括耐药性和研究差异,但新兴技术,如低温电子显微镜和CRISPR编辑,为更深入的探索提供了新的途径。专家意见:SQLE是一个尚未开发但有前景的治疗靶点,与氧化应激,铁下垂和肠道微生物群研究特别相关。通过先进的技术和多学科战略克服当前的障碍,可以推动sqle靶向治疗进入临床实践,支持精准医学和更广泛的转化应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.90
自引率
1.70%
发文量
58
审稿时长
3 months
期刊介绍: The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials. The Editors welcome: Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development. Articles should not include clinical information including specific drugs and clinical trials. Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs. The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.
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