General control non-derepressible 2（GCN2）屬于一種壓力應(yīng)答絲氨酸/蘇氨酸激酶，在整合應(yīng)激反應(yīng)（ISR）中負(fù)責(zé)感受氨基酸缺乏應(yīng)激后產(chǎn)生一系列反應(yīng)。GCN2的激活對(duì)于細(xì)胞的氧化應(yīng)激、增殖、自噬、凋亡、免疫、蛋白質(zhì)毒性和血管生成等均有關(guān)鍵的調(diào)節(jié)作用，與腫瘤、心肌損傷、肺纖維化等的發(fā)生發(fā)展有一定的相關(guān)性。綜述GCN2的生物學(xué)功能、結(jié)構(gòu)特征、作用機(jī)制和疾病關(guān)聯(lián)性，并總結(jié)分析GCN2抑制劑或激動(dòng)劑的研發(fā)現(xiàn)狀，重點(diǎn)闡述GCN2抑制劑或激動(dòng)劑在抗腫瘤方向的臨床應(yīng)用潛力，為靶向GCN2激酶的新藥開(kāi)發(fā)提供參考。

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

中國(guó)醫(yī)學(xué)科學(xué)院醫(yī)學(xué)與健康科技創(chuàng)新工程國(guó)家醫(yī)學(xué)健康科技戰(zhàn)略平臺(tái)與體系建設(shè)專(zhuān)項(xiàng)項(xiàng)目資助（2022-I2M-2-003）