靶向PI3K/AKT/mTOR信号通路治疗人类疾病：现状、趋势与解决方案
Targeting the PI3K/AKT/mTOR Signaling Pathway in the Treatment of Human Diseases: Current Status, Trends, and Solutions.
作者信息
Huang Jindi, Chen Liye, Wu Jiangxia, Ai Daiqiao, Zhang Ji-Quan, Chen Tie-Gen, Wang Ling
机构信息
Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, Joint International Research Laboratory of Synthetic Biology and Medicine, Guangdong Provincial Engineering and Technology Research Center of Biopharmaceuticals, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.
College of Pharmacy, Guizhou Medical University, Guiyang 550004, China.
出版信息
J Med Chem. 2022 Dec 22;65(24):16033-16061. doi: 10.1021/acs.jmedchem.2c01070. Epub 2022 Dec 12.
The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is one of the most important intracellular pathways involved in cell proliferation, growth, differentiation, and survival. Therefore, this route is a prospective biological target for treating various human diseases, such as tumors, neurodegenerative diseases, pulmonary fibrosis, and diabetes. An increasing number of clinical studies emphasize the necessity of developing novel molecules targeting the PI3K/AKT/mTOR pathway. This review focuses on recent advances in ATP-competitive inhibitors, allosteric inhibitors, covalent inhibitors, and proteolysis-targeting chimeras against the PI3K/AKT/mTOR pathway, and highlights possible solutions for overcoming the toxicities and acquired drug resistance of currently available drugs. We also provide recommendations for the future design and development of promising drugs targeting this pathway.
磷酸肌醇3激酶（PI3K）/蛋白激酶B（AKT）/雷帕霉素哺乳动物靶点（mTOR）信号通路是参与细胞增殖、生长、分化和存活的最重要的细胞内信号通路之一。因此，该信号通路是治疗各种人类疾病（如肿瘤、神经退行性疾病、肺纤维化和糖尿病）的一个潜在生物学靶点。越来越多的临床研究强调开发靶向PI3K/AKT/mTOR信号通路的新型分子的必要性。本综述重点介绍了针对PI3K/AKT/mTOR信号通路的ATP竞争性抑制剂、变构抑制剂、共价抑制剂和蛋白酶靶向嵌合体的最新进展，并强调了克服现有药物毒性和获得性耐药性的可能解决方案。我们还为未来设计和开发靶向该信号通路的有前景的药物提供了建议。
Zotero 插件