新型2-喹诺酮类衍生物作为SHP2抑制剂的设计、合成及生物活性研究
Design, Synthesis, and Bioactivity Study of Novel 2-Quinolone Derivatives as SHP2 Inhibitors
DOI: 10.12677/hjmce.2026.141009, PDF,   
作者: 张震轩, 曹 晴, 王文龙*：江南大学生命科学与健康工程学院，江苏 无锡
关键词: SHP2抑制剂；2-喹诺酮；变构抑制剂；SHP2 Inhibitors； 2-Quinolone； Allosteric Inhibitors
摘要: 蛋白酪氨酸磷酸酶2 (SHP2)在RAS/MAPK、PI3K/AKT等信号通路起着关键调控作用，其功能异常与多种肿瘤的发生发展密切相关，是重要的抗肿瘤靶点。本研究基于喹诺酮类化合物的抗肿瘤活性及SHP2变构口袋的结构特征，设计合成了一系列新型2-喹诺酮类衍生物，并进行了结构表征及生物活性评价。其中，代表化合物8b已通过分子对接初步探究了其与SHP2蛋白变构位点的结合模式。本研究为后续开发基于2-喹诺酮骨架的SHP2变构抑制剂提供了先导化合物与理论基础。
Abstract: Protein tyrosine phosphatase 2 (SHP2) plays a key role in several signaling pathways such as RAS/MAPK and PI3K/AKT. As an important anti-tumor target, its abnormal expression is associated with the development of various tumors. Based on the antitumor activity of quinolone compounds and the characteristics of the SHP2 allosteric pocket, this work designed and synthesized a series of novel 2-quinolone derivatives, followed by structural characterization and bioactivity evaluation. Among these, the binding mode between the allosteric site of protein SHP2 and representative compound 8b was investigated by molecular docking. This work provides lead compounds and theoretical foundations for the subsequent development of 2-quinolone-based allosteric inhibitors of SHP2.
文章引用：张震轩, 曹晴, 王文龙. 新型2-喹诺酮类衍生物作为SHP2抑制剂的设计、合成及生物活性研究[J]. 药物化学, 2026, 14(1): 89-96. https://doi.org/10.12677/hjmce.2026.141009

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