General control non-derepressible 2（GCN2）属于一种压力应答丝氨酸/苏氨酸激酶，在整合应激反应（ISR）中负责感受氨基酸缺乏应激后产生一系列反应。GCN2的激活对于细胞的氧化应激、增殖、自噬、凋亡、免疫、蛋白质毒性和血管生成等均有关键的调节作用，与肿瘤、心肌损伤、肺纤维化等的发生发展有一定的相关性。综述GCN2的生物学功能、结构特征、作用机制和疾病关联性，并总结分析GCN2抑制剂或激动剂的研发现状，重点阐述GCN2抑制剂或激动剂在抗肿瘤方向的临床应用潜力，为靶向GCN2激酶的新药开发提供参考。

GCN2 is a kind of to a stress-responsive serine/threonine kinase, which is responsible for sensing a series of responses after amino acid deficiency stress in the integrative stress response. The activation of GCN2 plays a key regulatory role in cellular oxidative stress, proteotoxicity, angiogenesis, proliferation, autophagy, apoptosis, immunity, and has a certain correlation with the occurrence and development of tumours, myocardial injury, lung fibrosis, etc. This article reviews the biological functions, structural characteristics, mechanism of action, disease relevance, and it also analyses the status quo of research on GCN2 inhibitors or agonists and focus on highlighting the clinical application potential of GCN2 inhibitors or agonists in the field of cancer treatment. So as to provide a reference for the development of new drugs targeting GCN2 kinase.

R979.1

中国医学科学院医学与健康科技创新工程国家医学健康科技战略平台与体系建设专项项目资助（2022-I2M-2-003）