首页|Benzo[ d]isoxazole Derivatives as Hypoxia-Inducible Factor (HIF)-1α Inhibitors
Benzo[ d]isoxazole Derivatives as Hypoxia-Inducible Factor (HIF)-1α Inhibitors
扫码查看
点击上方二维码区域，可以放大扫码查看
原文链接
NSTL
Amer Chemical Soc
? 2022 American Chemical Society. All rights reserved.Hypoxia-inducible factor, also known as HIF, is a transcriptional factor universally found in mammalian cells. HIF-1 is one of the HIF-families and acts as a heterodimer consisting of α and β subunits. It is found to play significant roles in pathologic conditions such as tumor development and metastasis. Here, we first report benzo[d]isoxazole analogues as HIF-1α transcription inhibitors. Thereby, we designed and synthesized 26 benzo[d]isoxazole derivatives and evaluated their inhibitory activities against HIF-1α transcription in HEK293T cells by a dual-luciferase gene reporter assay. Among them, compounds 15 and 31 showed the best efficacy in a cell-based assay with an IC50value of 24 nM and have potential antitumor effects for further development.
Department of Medicinal Chemistry School of Pharmacy Fudan University
Key Laboratory of Cell Differentiation and Apoptosis Chinese Ministry of Education Faculty of Basic Medicine Shanghai Jiao Tong University School of Medicine
NSTL
Amer Chemical Soc
