9QWG

X-ray structure of furin (PCSK3) in complex with the biphenyl-derived compound 24 (mi3140)

これはPDB形式変換不可エントリーです。

9QWG の概要

• エントリーDOI: 10.2210/pdb9qwg/pdb
• 分子名称: Furin, methyl 2-[1-[[3-[3,5-bis(chloranyl)phenyl]-5-[[4-(2-methoxy-2-oxidanylidene-ethyl)piperidin-1-yl]methyl]phenyl]methyl]piperidin-4-yl]ethanoate, CALCIUM ION, ... (8 entities in total)
• 機能のキーワード: furin, proprotein convertase subtilisin/kexin type 3, pcsk3, antiviral, inhibitor, protease, complex, hydrolase
• 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: 53887.79

構造登録者

Dahms, S.O.,Brandstetter, H. (登録日: 2025-04-14, 公開日: 2025-12-24)

主引用文献

Lange, R.W.,Boller, C.,Loresch, M.,Bloch, K.,Bottcher-Friebertshauser, E.,Brandstetter, H.,Dahms, S.O.,Steinmetzer, T.
Design, Synthesis, and Characterization of Dichlorobiphenyl-Derived Inhibitors of the Proprotein Convertase Furin.
J.Med.Chem., 68:25157-25170, 2025

PubMed Abstract: The proprotein convertase (PC) furin emerged as promising drug target for the treatment of numerous infectious diseases, cancer and cystic fibrosis. A recently described nonpeptidic lead structure served as template to develop a new series of PC inhibitors containing a dichlorobiphenyl-derived core segment decorated with a left and right inhibitor arm. The compounds were tested for their inhibitory potency against furin and the structurally related PC7. The most potent compounds inhibited furin with values <5 nM, whereas most of them were significantly weaker inhibitors of PC7. Only for one compound, a significant potency with a value of 7.3 nM against PC7 was found. Furthermore, crystal structures of six inhibitors in complex with furin were determined. Selected inhibitors were additionally tested for their antiviral potency against the furin-dependent H7N7 influenza A strain SC35M; a significant antiviral potency was found for compound .

PubMed: 41319212
DOI: 10.1021/acs.jmedchem.5c02157

実験手法

X-RAY DIFFRACTION (1.6 Å)