4TYD

Structure-based design of a novel series of azetidine inhibitors of the hepatitis C virus NS3/4A serine protease

4TYD の概要

• エントリーDOI: 10.2210/pdb4tyd/pdb
• 分子名称: NS3 protease, ZINC ION, (4R,6S,7Z,15S,17S)-17-[({7-methoxy-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl}oxy)methyl]-13-methyl-N-[(1-methylcyclopropyl)sulfonyl]-2,14-dioxo-1,3,13-triazatricyclo[13.2.0.0~4,6~]heptadec-7-ene-4-carboxamide, ... (5 entities in total)
• 機能のキーワード: structure-based design, hcv ns3/4a serine protease, azetidine inhibitors, proteros biostructures gmbh, hydrolase
• 由来する生物種: Hepatitis C virus (isolate 1)
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 267727.95

構造登録者

Parsy, C. (登録日: 2014-07-08, 公開日: 2014-09-10, 最終更新日: 2024-05-08)

主引用文献

Parsy, C.,Alexandre, F.R.,Brandt, G.,Caillet, C.,Cappelle, S.,Chaves, D.,Convard, T.,Derock, M.,Gloux, D.,Griffon, Y.,Lallos, L.,Leroy, F.,Liuzzi, M.,Loi, A.G.,Moulat, L.,Musiu, C.,Rahali, H.,Roques, V.,Seifer, M.,Standring, D.,Surleraux, D.
Structure-based design of a novel series of azetidine inhibitors of the hepatitis C virus NS3/4A serine protease.
Bioorg.Med.Chem.Lett., 24:4444-4449, 2014

PubMed Abstract: Structural homology between thrombin inhibitors and the early tetrapeptide HCV protease inhibitor led to the bioisosteric replacement of the P2 proline by a 2,4-disubstituted azetidine within the macrocyclic β-strand mimic. Molecular modeling guided the design of the series. This approach was validated by the excellent activity and selectivity in biochemical and cell based assays of this novel series and confirmed by the co-crystal structure of the inhibitor with the NS3/4A protein (PDB code: 4TYD).

PubMed: 25155387
DOI: 10.1016/j.bmcl.2014.08.002

実験手法

X-RAY DIFFRACTION (2.84 Å)