6JMF

Crystal structure of human tyrosine-protein kinase Fes/Fps in complex with compound 4

6JMF の概要

• エントリーDOI: 10.2210/pdb6jmf/pdb
• 分子名称: Tyrosine-protein kinase Fes/Fps, SULFATE ION, 6-{[(1R,2S)-2-aminocyclohexyl]amino}-5-cyano-2-[(3-methylphenyl)amino]pyridine-3-carboxamide, ... (4 entities in total)
• 機能のキーワード: fes, c-fes, tyrosine protein kinase, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43040.24

構造登録者

Baba, D.,Hanzawa, H. (登録日: 2019-03-08, 公開日: 2019-06-12, 最終更新日: 2023-11-22)

主引用文献

Taniguchi, T.,Inagaki, H.,Baba, D.,Yasumatsu, I.,Toyota, A.,Kaneta, Y.,Kiga, M.,Iimura, S.,Odagiri, T.,Shibata, Y.,Ueda, K.,Seo, M.,Shimizu, H.,Imaoka, T.,Nakayama, K.
Discovery of Novel Pyrido-pyridazinone Derivatives as FER Tyrosine Kinase Inhibitors with Antitumor Activity.
Acs Med.Chem.Lett., 10:737-742, 2019

PubMed Abstract: To obtain a new anticancer drug, we focused on FER tyrosine kinase. Starting with high-throughput screening with our in-house chemical library, compound , which has a pyridine moiety, was found. Referring to their X-ray crystal structure with FES proto-oncogene tyrosine kinase, as a surrogate of FER followed by chemical modification including scaffold hopping of the pyridine template, we discovered pyrido-pyridazinone derivatives with potent FER kinase inhibitory activity. Here, we disclose the structure-activity relationship on the scaffold and representative compound (), which showed antitumor efficacy in a subcutaneous tumor model.

PubMed: 31097992
DOI: 10.1021/acsmedchemlett.8b00631

実験手法

X-RAY DIFFRACTION (2 Å)