Joint Research Institution of Altitude Health, Department of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
College of Life Sciences, Sichuan University, Chengdu, Sichuan 610064, China.
J Med Chem. 2023 Feb 23;66(4):2257-2281. doi: 10.1021/acs.jmedchem.2c01523. Epub 2023 Feb 6.
CK2 (casein kinase 2) is a serine/threonine protein kinase that is ubiquitous in eukaryotic cells and plays important roles in a variety of cellular functions, including cell growth, apoptosis, circadian rhythms, DNA damage repair, transcription, and translation. CK2 is involved in cancer pathogenesis and the occurrence of many diseases. Therefore, targeting CK2 is a promising therapeutic strategy. Although many CK2-specific small-molecule inhibitors have been developed, only CX-4945 has progressed to clinical trials. In recent years, novel CK2 inhibitors have gradually become a research hotspot, which is expected to overcome the limitations of traditional inhibitors. Herein, we summarize the structure, biological functions, and disease relevance of CK2 and emphatically analyze the structure-activity relationship (SAR) and binding modes of small-molecule CK2 inhibitors. We also discuss the latest progress of novel strategies, providing insights into new drugs targeting CK2 for clinical practice.
CK2（酪蛋白激酶 2）是一种丝氨酸/苏氨酸蛋白激酶，在真核细胞中普遍存在，在多种细胞功能中发挥重要作用，包括细胞生长、细胞凋亡、昼夜节律、DNA 损伤修复、转录和翻译。CK2 参与癌症发病机制和许多疾病的发生。因此，靶向 CK2 是一种有前途的治疗策略。尽管已经开发出许多 CK2 特异性小分子抑制剂，但只有 CX-4945 已进入临床试验阶段。近年来，新型 CK2 抑制剂逐渐成为研究热点，有望克服传统抑制剂的局限性。本文总结了 CK2 的结构、生物学功能和疾病相关性，并着重分析了小分子 CK2 抑制剂的结构-活性关系（SAR）和结合模式。我们还讨论了新型策略的最新进展，为针对 CK2 的新药研发提供了临床实践的思路。
