- 著者
- Kazuma Kaitoh Aki Nakatsu Shuichi Mori Hiroyuki Kagechika Yuichi Hashimoto Shinya Fujii
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.67, no.6, pp.566-575, 2019-06-01 (Released:2019-06-01)
- 参考文献数
- 33
- 被引用文献数
- 9
We report here the development of phenylamino-1,3,5-triazine derivatives as novel nonsteroidal progesterone receptor (PR) antagonists. PR plays key roles in various physiological systems, including the female reproductive system, and PR antagonists are promising candidates for clinical treatment of multiple diseases. By using the phenylamino-1,3,5-triazine scaffold as a template structure, we designed and synthesized a series of 4-cyanophenylamino-1,3,5-triazine derivatives. The synthesized compounds exhibited PR antagonistic activity, and among them, compound 12n was the most potent (IC50 = 0.30 µM); it also showed significant binding affinity to the PR ligand-binding domain. Docking simulation supported the design rationale of the compounds. Our results suggest that the phenylamino-1,3,5-triazine scaffold is a versatile template for development of nonsteroidal PR antagonists and that the developed compounds are promising lead compounds for further structural development of nonsteroidal PR antagonists.
- 著者
- Kosuke Chiba Yuichi Hashimoto Takao Yamaguchi
- 出版者
- 公益社団法人日本薬学会
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.65, no.10, pp.994-996, 2017-10-01 (Released:2017-10-01)
- 参考文献数
- 16
- 被引用文献数
- 3
We recently developed 4-azidophthalimide (AzPI) as a compact fluorogenic photoreactive tag that can be attached to ligands to achieve selective fluorescence labeling of target proteins even in the presence of a large excess of non-target proteins. To further establish the utility of the AzPI tag, we focused here on streptavidin labeling with biotin–AzPI conjugates, and evaluated the relation between the amount of covalently labeled streptavidin (labeling rate) and fluorescence intensity. The labeling rate was proportional to the fluorescence intensity under standardized photo-irradiation conditions. Prolongation of the photo-irradiation time led to a marked increase in the labeling rate, but this was accompanied by a gradual decrease in the fluorescence intensity, which appeared to be due at least in part to photo-induced degradation of the target streptavidin. These findings should be helpful for achieving sensitive fluorescence detection of target proteins by using the AzPI tag.
- 著者
- 橋本 雄一 都築 誉史 ハシモト ユウイチ ツズキ タカシ Yuichi Hashimoto Tsuzuki Takashi
- 雑誌
- 立教大学心理学研究
- 巻号頁・発行日
- vol.55, pp.45-54, 2013-03-31
- 著者
- 橋本 雄一 都築 誉史 ハシモト ユウイチ ツズキ タカシ Yuichi Hashimoto Tsuzuki Takashi
- 出版者
- 立教大学心理学研究室
- 雑誌
- 立教大学心理学研究 (ISSN:13462032)
- 巻号頁・発行日
- no.55, pp.45-53, 2013