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Benzo[ d ]isoxazole Derivatives as Hypoxia-Inducible Factor (HIF)-1α Inhibitors.
- Source :
-
ACS medicinal chemistry letters [ACS Med Chem Lett] 2022 Sep 13; Vol. 13 (12), pp. 1864-1869. Date of Electronic Publication: 2022 Sep 13 (Print Publication: 2022). - Publication Year :
- 2022
-
Abstract
- 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 IC <subscript>50</subscript> value of 24 nM and have potential antitumor effects for further development.<br />Competing Interests: The authors declare no competing financial interest.<br /> (© 2022 American Chemical Society.)
Details
- Language :
- English
- ISSN :
- 1948-5875
- Volume :
- 13
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- ACS medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 36518694
- Full Text :
- https://doi.org/10.1021/acsmedchemlett.2c00308