噻唑腙类IGF2BP2小分子抑制剂的设计、合成及生物活性研究  

Design,synthesis and biological activity study of thiazolehydrazonebased small molecule inhibitors of IGF2BP2

作　　者：张诗迪 马赛 王颖哲 蔡媛倩 张艳[1,2] 尤启冬 郭小可[1,2] ZHANG Shi-di;MA Sai;WANG Ying-zhe;CAI Yuan-qian;ZHANG Yan;YOU Qi-dong;GUO Xiao-ke(Jiangsu Key Laboratory of Drug Design and Optimization,China Pharmaceutical University,Nanjing 210009,China;School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学,江苏省药物分子设计与成药性优化重点实验室,江苏南京210009 [2]中国药科大学药学院,江苏南京210009

出　　处：《药学学报》2024年第11期3006-3016,共11页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(82173673,82473789)。

摘　　要：胰岛素样生长因子2 mRNA结合蛋白2(insulin-like growth factor 2 mRNA binding protein 2,IGF2BP2)是N^(6)-甲基腺苷(N^(6)-methyladenosine,m^(6)A)的识别蛋白,介导了下游mRNA的稳定性,是极具前景的抗肿瘤靶点。本研究基于课题组前期筛选的先导化合物1g,以噻唑腙作为母核设计并合成了52个IGF2BP2小分子抑制剂,其中9g、10g、37g、47g和52g等具有较好的靶标活性。该项工作是以噻唑腙为母核发展IGF2BP2小分子抑制剂的一次探索,为后续相关研究奠定基础。Insulin-like growth factor 2 mRNA binding protein 2(IGF2BP2)is a recognition protein for N^(6)-methyladenosine(m^(6)A),mediating the stability of downstream mRNA,and is a promising anti-tumor target.Based on the lead compound 1g from previous screening,this study designed and synthesized 52 IGF2BP2 small molecule inhibitors using thiazole hydrazone as the parent nucleus.Among them,9g,10g,37g,47g and 52g showed good inhibitory activities.This work represents an initial exploration in the development of small molecule inhibitors targeting IGF2BP2,using thiazolehydrazone as the core structure.It lays a foundation for subsequent related research.

关 键 词：噻唑腙衍生物 胰岛素样生长因子2 mRNA结合蛋白2 N6-甲基腺苷 小分子抑制剂 设计合成 

分 类 号：R914[医药卫生—药物化学]