4MZ4

Discovery of an Irreversible HCV NS5B Polymerase Inhibitor

4MZ4 の概要

• エントリーDOI: 10.2210/pdb4mz4/pdb
• 分子名称: RNA-directed RNA polymerase, 1-[(2-chloroquinolin-3-yl)methyl]-6-fluoro-5-methyl-3-(2-oxo-1,2-dihydropyridin-3-yl)-1H-indole-2-carboxylic acid, PHOSPHATE ION, ... (4 entities in total)
• 機能のキーワード: rna-dependent rna polymerase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Hepatitis C virus (HCV)
• 細胞内の位置: Core protein p21: Host endoplasmic reticulum membrane; Single-pass membrane protein (By similarity). Core protein p19: Virion (By similarity). Envelope glycoprotein E1: Virion membrane; Single-pass type I membrane protein (Potential). Envelope glycoprotein E2: Virion membrane; Single-pass type I membrane protein (Potential). p7: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Protease NS2-3: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 5A: Host endoplasmic reticulum membrane; Peripheral membrane protein (By similarity). RNA-directed RNA polymerase: Host endoplasmic reticulum membrane; Single-pass type I membrane protein (Potential): O92972
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 129591.82

構造登録者

Zeng, Q.,Anilkumar, G.N.,Rosenblum, S.B.,Huang, H.-C.,Lesburg, C.A.,Jiang, Y.,Selyutin, O.,Chan, T.-Y.,Bennett, F.,Chen, K.X.,Venkatraman, S.,Sannigrahi, M.,Velazquez, F.,Duca, J.S.,Gavalas, S.,Huang, Y.,Pu, H.,Wang, L.,Pinto, P.,Vibulbhan, B.,Agrawal, S.,Ferrari, E.,Jiang, C.-K.,Li, C.,Hesk, D.,Gesell, J.,Sorota, S.,Shih, N.-Y.,Njoroge, F.G.,Kozlowski, J.A. (登録日: 2013-09-29, 公開日: 2013-12-11, 最終更新日: 2024-11-06)

主引用文献

Zeng, Q.,Nair, A.G.,Rosenblum, S.B.,Huang, H.C.,Lesburg, C.A.,Jiang, Y.,Selyutin, O.,Chan, T.Y.,Bennett, F.,Chen, K.X.,Venkatraman, S.,Sannigrahi, M.,Velazquez, F.,Duca, J.S.,Gavalas, S.,Huang, Y.,Pu, H.,Wang, L.,Pinto, P.,Vibulbhan, B.,Agrawal, S.,Ferrari, E.,Jiang, C.K.,Li, C.,Hesk, D.,Gesell, J.,Sorota, S.,Shih, N.Y.,Njoroge, F.G.,Kozlowski, J.A.
Discovery of an irreversible HCV NS5B polymerase inhibitor.
Bioorg.Med.Chem.Lett., 23:6585-6587, 2013

PubMed Abstract: The discovery of lead compound 2e was described. Its covalent binding to HCV NS5B polymerase enzyme was investigated by X-ray analysis. The results of distribution, metabolism and pharmacokinetics were reported. Compound 2e was demonstrated to be potent (replicon GT-1b EC50 = 0.003 μM), highly selective, and safe in in vitro and in vivo assays.

PubMed: 24252545
DOI: 10.1016/j.bmcl.2013.10.060

実験手法

X-RAY DIFFRACTION (1.63 Å)