UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
FEBS J. 2023 Jun;290(11):2845-2864. doi: 10.1111/febs.16442. Epub 2022 Mar 31.
Kinases are key regulatory signalling proteins governing numerous essential biological processes and cellular functions. Dysregulation of many protein kinases is associated with cancer initiation and progression. Given their crucial roles, there has been increasing interest in harnessing kinases as prospective drug targets for cancer. In recent decades, numerous small-molecule kinase inhibitors have been developed and revolutionized the cancer treatment landscape. Despite their great potential, challenges remain in developing highly selective and effective kinase inhibitors, with toxicity and resistance issues frequently arising. In this review, we first provide an overview of the role of kinases in carcinogenesis and describe the current progress with small-molecule kinase inhibitors that have been approved for clinical use. We then discuss the application of mass spectrometry (MS)-based proteomics strategies to help in the design of kinase inhibitors. Finally, we discuss the challenges and outlook concerning MS-based proteomics techniques for kinase drug research.
激酶是调节众多重要生物过程和细胞功能的关键信号蛋白。许多蛋白激酶的失调与癌症的发生和发展有关。鉴于它们的重要作用，人们越来越有兴趣将激酶作为癌症的潜在药物靶点。在过去的几十年中，已经开发出了许多小分子激酶抑制剂，彻底改变了癌症治疗的格局。尽管它们具有巨大的潜力，但在开发高度选择性和有效的激酶抑制剂方面仍然存在挑战，经常出现毒性和耐药性问题。在这篇综述中，我们首先概述了激酶在致癌作用中的作用，并描述了已被批准用于临床使用的小分子激酶抑制剂的最新进展。然后，我们讨论了基于质谱（MS）的蛋白质组学策略在激酶抑制剂设计中的应用。最后，我们讨论了基于 MS 的蛋白质组学技术在激酶药物研究中的挑战和前景。
