4U01

HCV NS3/4A serine protease in complex with 6570

4U01 の概要

• エントリーDOI: 10.2210/pdb4u01/pdb
• 分子名称: Non-structural 3 protease, NS4A protein, (2S,3aS,10Z,11aS,12aR)-2-({8-fluoro-7-methoxy-2-[4-(propan-2-yl)-1,3-thiazol-2-yl]quinolin-4-yl}oxy)-5-methyl-N-[(1-methylcyclopropyl)sulfonyl]-4,14-dioxo-1,2,3,3a,4,5,6,7,8,9,11a,12,13,14-tetradecahydro-12aH-cyclopropa[m]pyrrolo[1,2-c][1,3,6]triazacyclotetradecine-12a-carboxamide, ... (5 entities in total)
• 機能のキーワード: hvc, ns3/4a protease, drug design, proteros biostructures gmbh, hydrolase
• 由来する生物種: Hepatitis C virus (isolate Con1); 詳細
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 215982.08

構造登録者

Parsy, C.C.,Alexandre, F.-R.,Brandt, G.,Caillet, C.,Chaves, D.,Derock, M.,Gloux, D.,Griffon, Y.,Lallos, L.B.,Leroy, F.,Liuzzi, M.,Loi, A.-G.,Mayes, B.,Moulat, L.,Moussa, A.,Chiara, M.,Roques, V.,Rosinovsky, E.,Seifer, M.,Stewart, A.,Wang, J.,Standring, D.,Surleraux, D. (登録日: 2014-07-11, 公開日: 2015-07-29, 最終更新日: 2024-05-08)

主引用文献

Parsy, C.C.,Alexandre, F.R.,Bidau, V.,Bonnaterre, F.,Brandt, G.,Caillet, C.,Cappelle, S.,Chaves, D.,Convard, T.,Derock, M.,Gloux, D.,Griffon, Y.,Lallos, L.B.,Leroy, F.,Liuzzi, M.,Loi, A.G.,Moulat, L.,Chiara, M.,Rahali, H.,Roques, V.,Rosinovsky, E.,Savin, S.,Seifer, M.,Standring, D.,Surleraux, D.
Discovery and structural diversity of the hepatitis C virus NS3/4A serine protease inhibitor series leading to clinical candidate IDX320.
Bioorg.Med.Chem.Lett., 25:5427-5436, 2015

PubMed Abstract: Exploration of the P2 region by mimicking the proline motif found in BILN2061 resulted in the discovery of two series of potent HCV NS3/4A protease inhibitors. X-ray crystal structure of the ligand in contact with the NS3/4A protein and modulation of the quinoline heterocyclic region by structure based design and modeling allowed for the optimization of enzyme potency and cellular activity. This research led to the selection of clinical candidate IDX320 having good genotype coverage and pharmacokinetic properties in various species.

PubMed: 26410074
DOI: 10.1016/j.bmcl.2015.09.009

実験手法

X-RAY DIFFRACTION (2.8 Å)