期刊
MOLECULES
卷 23, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/molecules23040885
关键词
hypoxia inducible factor; factor inhibiting hypoxia inducible factor; furan; thiophene
资金
- Platforms for Drug Discovery, Informatics, and Structural Life Science (PDIS) from the MEXT
- Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED [JP17am0101095]
- JSPS KAKENHI grant [26860168, 16H05922, 17K19916]
- Adaptable and Seamless Technology transfer Program through target driven R&D (A-STEP), Japan Science and Technology Agency grant [J120001909]
- [24-5784]
- Grants-in-Aid for Scientific Research [26860168, 17K19916, 16H05922, 16H04138] Funding Source: KAKEN
Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-alpha (HIF-alpha) is a major transcription factor that orchestrates this protective effect. To activate HIF exogenously, without exposing cells to hypoxic conditions, many small-molecule inhibitors targeting prolyl hydroxylase domain-containing protein have been developed. In addition, suppression of factor inhibiting HIF-1 (FIH-1) has also been shown to have the potential to activate HIF-alpha. However, few small-molecule inhibitors of FIH-1 have been developed. In this study, we synthesized a series of furan-and thiophene-2-carbonyl amino acid derivatives having the potential to inhibit FIH-1. The inhibitory activities of these compounds were evaluated in SK-N-BE(2) c cells by measuring HIF response element (HRE) promoter activity. Several furan-and thiophene-2-carbonyl amino acid derivatives inhibited FIH-1 based on correlations among the docking score of the FIH-1 active site, the chemical structure of the compounds, and biological HIF-alpha/HRE transcriptional activity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据