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Benzo[d]isoxazole Derivatives as Hypoxia-Inducible Factor (HIF)-1α Inhibitors.

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 IC₅₀ value of 24 nM and have potential antitumor effects for further development.

SUBMITTER: Xue Z

PROVIDER: S-EPMC9743424 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Benzo[d]isoxazole Derivatives as Hypoxia-Inducible Factor (HIF)-1α Inhibitors.

Xue Zian Z Li Huiti H Xie Wenhao W Xu Ying Y Zhou Lu L Qu Zhi-Bei ZB

ACS medicinal chemistry letters 20220913 12

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 inh ...[more]

PMID: 36518694

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