抗肿瘤联合司他汀类药物的新生命：混合药、原药、联合疗法和抗体-药物共轭物的最新进展

IF 6 2区医学 Q1 CHEMISTRY, MEDICINAL

European Journal of Medicinal Chemistry Pub Date : 2024-10-31 DOI:10.1016/j.ejmech.2024.117021

Marialuigia Fantacuzzi, Simone Carradori, Letizia Giampietro, Cristina Maccallini, Barbara De Filippis, Rosa Amoroso, Alessandra Ammazzalorso

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引用次数: 0

摘要

自从从天然资源中发现考布他汀类化合物以来，人们一直在广泛研究其强大的细胞毒性作用，以便将其应用于抗肿瘤治疗。然而，由于低水溶性和双键构型的化学不稳定性等主要的药代动力学问题，阻碍了它们在治疗中的应用。为了更安全地使用考布他汀类药物作为抗癌药物，人们一直在努力寻找新的策略。这篇综述分析了联合司他汀类药物研究的最新进展，其特点是发现了混合药物、原药和新型联合疗法。有趣的是，最近有人提出将强效细胞毒性药物考布他汀 A4（CA4）作为构建新型抗体-药物共轭物（ADCs）的有效载荷，从而使细胞毒性药物有效靶向特定肿瘤。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

A novel life for antitumor combretastatins: Recent developments of hybrids, prodrugs, combination therapies, and antibody-drug conjugates

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A novel life for antitumor combretastatins: Recent developments of hybrids, prodrugs, combination therapies, and antibody-drug conjugates

Since their discovery from natural sources, the potent cytotoxic effects of combretastatins were widely studied for the application in antitumor therapy. However, major pharmacokinetic issues as low water solubility and chemical instability of the double bond configuration prevented their use in therapy. A lot of efforts have been directed towards the search of novel strategies, allowing a safer use of combretastatins as anticancer agents. This review analyses the recent landscape in combretastatin research, characterized by the identification of hybrids, prodrugs, and novel combination treatments. Interestingly, the potent cytotoxic agent combretastatin A4 (CA4) was recently proposed as payload in the construction of novel antibody-drug conjugates (ADCs), allowing an efficient targeting of the cytotoxic agent to specific tumors.

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来源期刊

European Journal of Medicinal Chemistry 化学-医药化学

CiteScore

11.70

自引率

9.00%

发文量

863

审稿时长

29 days

期刊介绍： The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers. A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.