药物发现
铅化合物
化学
肺癌
癌症研究
RNA剪接
外显子
癌症
计算生物学
生物
遗传学
生物化学
基因
医学
核糖核酸
体外
病理
作者
Bo Ra Lee,Dae Gyu Kim,Young Mi Kim,Sung Hoon Kim,Inhee Choi
标识
DOI:10.1016/j.bmcl.2022.128889
摘要
Aminoacyl-tRNA synthetase (ARS) interacting multifunctional protein2 (AIMP2) plays a vital role in protein synthesis. However, a splicing variant in which the second of the four exons of AIMP2 is deleted, inhibits the tumor suppression activity of AIMP2. Herein, we describe our discovery of series of potent AIMP2-DX2 inhibitors that are targeting lung cancer. Optimization of series using ligand-based drug design strategy led to discovery of compound 35, a potent AIMP2-DX2 inhibitor that is the most efficacious in H460 and A549 cells. This benzodioxane series may represent good starting points for further lead optimization of the identification potential drug candidates for the AIMP2-DX2 targeted treatment of lung cancer.
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