Lacal Juan Carlos, Zimmerman Tahl, Campos Joaquín M
Instituto de Investigaciones Biomédicas, CSIC, 28029 Madrid, Spain.
Instituto de Investigación Sanitaria Hospital La Paz, IDIPAZ, 28046 Madrid, Spain.
Pharmaceutics. 2021 May 25;13(6):788. doi: 10.3390/pharmaceutics13060788.
Choline kinase (ChoK) is a cytosolic enzyme that catalyzes the phosphorylation of choline to form phosphorylcholine (Cho) in the presence of ATP and magnesium. ChoK is required for the synthesis of key membrane phospholipids and is involved in malignant transformation in a large variety of human tumours. Active compounds against ChoK have been identified and proposed as antitumor agents. The ChoK inhibitory and antiproliferative activities of symmetrical bispyridinium and bisquinolinium compounds have been defined using quantitative structure-activity relationships (QSARs) and structural parameters. The design strategy followed in the development of the most active molecules is presented. The selective anticancer activity of these structures is also described. One promising anticancer compound has even entered clinical trials. Recently, ChoKα inhibitors have also been proposed as a novel therapeutic approach against parasites, rheumatoid arthritis, inflammatory processes, and pathogenic bacteria. The evidence for ChoKα as a novel drug target for approaches in precision medicine is discussed.
胆碱激酶（ChoK）是一种胞质酶，在ATP和镁存在的情况下，催化胆碱磷酸化形成磷酸胆碱（Cho）。ChoK是关键膜磷脂合成所必需的，并且参与多种人类肿瘤的恶性转化。已鉴定出针对ChoK的活性化合物，并将其作为抗肿瘤剂提出。已使用定量构效关系（QSAR）和结构参数确定了对称双吡啶鎓和双喹啉鎓化合物的ChoK抑制和抗增殖活性。介绍了在开发最具活性分子过程中遵循的设计策略。还描述了这些结构的选择性抗癌活性。一种有前景的抗癌化合物甚至已进入临床试验。最近，ChoKα抑制剂也被提议作为对抗寄生虫、类风湿性关节炎、炎症过程和病原菌的一种新型治疗方法。讨论了ChoKα作为精准医学方法中新型药物靶点的证据。
