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喹啉基小分子作为激酶抑制剂的最新进展(2020 - 2024年)

Recent Advances of Quinoline-Based Small Molecules as Kinase Inhibitors (2020-2024).

作者信息

Sultan Sara, Zenati Ruba A, Anbar Hanan S, El-Gamal Mohammed I, Semreen Mohammad H

机构信息

Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.

Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates.

出版信息

ChemMedChem. 2025 May 13:e2500279. doi: 10.1002/cmdc.202500279.

Abstract

Quinoline-containing compounds have gained prominence in drug discovery as versatile scaffolds. These compounds have shown promise in the development of kinase inhibitors, which are crucial treatment options used in various cancer cases. This review explores the recent advances from 2020 to 2024 in the design, synthesis, and optimization of quinoline-based kinase inhibitors, focusing on their role in targeting key kinases, implicated in cancer signaling pathways. Quinoline derivatives exhibit significant inhibitory activity across a broad spectrum of kinases, highlighting their potential to disrupt aberrant signaling that drives tumor growth and progression. Several FDA-approved quinoline-containing compounds are utilized in clinical settings as kinase inhibitors, reinforcing their importance and relevance in clinical oncology. This review compiles the pharmacological profiles of these inhibitors spotlighting key compounds that have demonstrated potent inhibitory activities, excellent selectivity profiles, and promising preclinical or clinical outcomes. The review also addresses the challenges associated with their development and discusses future directions for optimizing quinoline-based kinase inhibitors, such as leveraging advanced drug design techniques, exploring novel targets, and expanding their use in combination therapies. By summarizing recent advancements, this review aims to provide insights into the evolving landscape of quinoline-based kinase inhibitors and their potential as next-generation anticancer therapies.

摘要

含喹啉的化合物作为通用骨架在药物研发中备受关注。这些化合物在激酶抑制剂的开发中显示出前景,激酶抑制剂是用于各种癌症病例的关键治疗选择。本综述探讨了2020年至2024年基于喹啉的激酶抑制剂在设计、合成和优化方面的最新进展,重点关注它们在靶向参与癌症信号通路的关键激酶中的作用。喹啉衍生物在广泛的激酶中表现出显著的抑制活性,突出了它们破坏驱动肿瘤生长和进展的异常信号的潜力。几种FDA批准的含喹啉化合物在临床环境中用作激酶抑制剂,强化了它们在临床肿瘤学中的重要性和相关性。本综述汇编了这些抑制剂的药理学概况,重点介绍了已显示出强效抑制活性、优异选择性概况以及有前景的临床前或临床结果的关键化合物。该综述还讨论了与它们的开发相关的挑战,并探讨了优化基于喹啉的激酶抑制剂的未来方向,例如利用先进的药物设计技术、探索新靶点以及扩大它们在联合疗法中的应用。通过总结最近的进展,本综述旨在深入了解基于喹啉的激酶抑制剂的不断演变的格局及其作为下一代抗癌疗法的潜力。

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