|
|||||
|
|
| KRAS相关信号通路与小分子抑制剂研究进展 | |
| 引用本文： | 谭斌, 全旭, 李博. KRAS相关信号通路与小分子抑制剂研究进展[J]. 药学进展, 2021, 45(5): 382-392. |
| 作者姓名： | 谭斌 全旭 李博 |
| 作者单位： | 1.1. 中国药科大学药学院, 江苏 南京 211198 |
| 摘 要： | KRAS基因属于Ras基因家族，其编码的KRAS蛋白通过激活下游信号通路参与细胞增殖、分化及凋亡等生命活动的调控。某些KRAS基因突变会引起KRAS蛋白过度表达和持续活化，进而过度激活下游信号通路，导致细胞不可控制地增殖恶变，最终造成组织癌变。寻找KRAS突变相关肿瘤的治疗策略一直是研究热点之一，然而KRAS蛋白突变体是公认的难靶蛋白之一，其直接作用靶点的小分子抑制剂的设计具有很大的挑战性，目前尚无相关药物批准上市。通过对KRAS蛋白结构与功能、相关信号通路和突变体在肿瘤发生发展中的作用，以及相关小分子抑制剂的突破性研究进展进行综述，为进一步研发KRAS突变肿瘤治疗药物提供参考。 |
| 关 键 词： | KRAS蛋白突变 信号通路 抗肿瘤 小分子抑制剂 |
| 收稿时间： | 2020-07-01 |
Advances of Research on KRAS-related Signaling Pathways and Its Inhibitors |
|
| TAN Bin, QUAN Xu, LI Bo. Advances of Research on KRAS-related Signaling Pathways and Its Inhibitors[J]. Progress in Pharmaceutical Sciences, 2021, 45(5): 382-392. | |
| Authors: | TAN Bin QUAN Xu LI Bo |
| Affiliation: | 1.1. School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China |
| Abstract: | KRAS gene belongs to Ras gene family.Its coding protein controls cell proliferation, differentiation and apoptosis by activating downstream signaling pathways.Once KRAS gene mutates, KRAS proteins could be overexpressed and continuously activated, which in turn overactivates downstream signaling pathways, leading to uncontrollable cell proliferation and malignancy, and ultimately tissue canceration.Exploring therapeutic strategies for tumors related to KRAS mutations has always been one of the research hot spots.However, KRAS protein mutants have been recognized as one of the difficult kinds of target proteins.The design of small molecule inhibitors directly targeting KRAS protein mutants is very challenging, and there are no related drugs approved for marketing.Here, we briefly summarize the structure and function, related signaling pathways, role of mutants of KRAS in tumorigenesis and the developments of small molecule inhibitors of KRAS mutations, aiming to provide new ideas for the treatment of KRAS mutant cancers. |
| Keywords: | KRAS mutation signaling pathway antitumor small-molecule inhibitor |
| 点击此处可从《药学进展》浏览原始摘要信息 | |
| 点击此处可从《药学进展》下载全文 | |