6I13

CRYSTAL STRUCTURE OF FASCIN IN COMPLEX WITH COMPOUND 7

6I13 の概要

• エントリーDOI: 10.2210/pdb6i13/pdb
• 分子名称: Fascin, ACETATE ION, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: actin bundling, small molecule inhibition, structural protein
• 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: 55239.97

構造登録者

Schuettelkopf, A.W. (登録日: 2018-10-27, 公開日: 2019-02-27, 最終更新日: 2024-01-24)

主引用文献

Francis, S.,Croft, D.,Schuttelkopf, A.W.,Parry, C.,Pugliese, A.,Cameron, K.,Claydon, S.,Drysdale, M.,Gardner, C.,Gohlke, A.,Goodwin, G.,Gray, C.H.,Konczal, J.,McDonald, L.,Mezna, M.,Pannifer, A.,Paul, N.R.,Machesky, L.,McKinnon, H.,Bower, J.
Structure-based design, synthesis and biological evaluation of a novel series of isoquinolone and pyrazolo[4,3-c]pyridine inhibitors of fascin 1 as potential anti-metastatic agents.
Bioorg.Med.Chem.Lett., 29:1023-1029, 2019

PubMed Abstract: Fascin is an actin binding and bundling protein that is not expressed in normal epithelial tissues but overexpressed in a variety of invasive epithelial tumors. It has a critical role in cancer cell metastasis by promoting cell migration and invasion. Here we report the crystal structures of fascin in complex with a series of novel and potent inhibitors. Structure-based elaboration of these compounds enabled the development of a series with nanomolar affinities for fascin, good physicochemical properties and the ability to inhibit fascin-mediated bundling of filamentous actin. These compounds provide promising starting points for fascin-targeted anti-metastatic therapies.

PubMed: 30773430
DOI: 10.1016/j.bmcl.2019.01.035

実験手法

X-RAY DIFFRACTION (1.79 Å)