日本語フィールド
著者：Kawaguchi, Shin ichi; Gonda, Yuhei; Yamamoto, Takuya; Sato, Yuki; Shinohara, Hiroyuki; Kobiki, Yohsuke; Ichimura, Atsuhiko; Dan, Takashi; Sonoda, Motohiro; Miyata, Toshio; Ogawa, Akiya; Tsujita, Tadayuki題名：Furan- and thiophene-2-carbonyl amino acid derivatives activate hypoxia-inducible factor via inhibition of factor inhibiting hypoxia-inducible factor-1発表情報：Molecules 巻: 23 号: 4 ページ: 885キーワード：概要：Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α) 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-α. 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-α/HRE transcriptional activity.抄録：英語フィールド
Author：Kawaguchi, Shin ichi; Gonda, Yuhei; Yamamoto, Takuya; Sato, Yuki; Shinohara, Hiroyuki; Kobiki, Yohsuke; Ichimura, Atsuhiko; Dan, Takashi; Sonoda, Motohiro; Miyata, Toshio; Ogawa, Akiya; Tsujita, TadayukiTitle：Furan- and thiophene-2-carbonyl amino acid derivatives activate hypoxia-inducible factor via inhibition of factor inhibiting hypoxia-inducible factor-1Announcement information:Molecules Vol: 23 Issue: 4 Page: 885An abstract：Induction of a series of anti-hypoxic proteins protects cells during exposure to hypoxic conditions. Hypoxia-inducible factor-α (HIF-α) 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-α. 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-α/HRE transcriptional activity.