4KHR

HCV NS5B GT1A C316Y with GSK5852

4KHR の概要

• エントリーDOI: 10.2210/pdb4khr/pdb
• 関連するPDBエントリー: 4KAI 4KB7 4KBI 4KE5 4KHM
• 分子名称: NS5B RNA-dependent RNA polymerase, SULFATE ION, [4-({[5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-6-yl](methylsulfonyl)amino}methyl)-2-fluorophenyl]boronic acid, ... (4 entities in total)
• 機能のキーワード: hcv polymerase, hcv ns5b, site iv inhibitor, boron, p66, p70, rna dependent rna polymerase, rna directed rna polymerase, polymerase, rns dependent rna polymerase, replication-replication inhibitor complex, replication/replication inhibitor
• 由来する生物種: Hepatitis C virus subtype 1a (HCV)
• 細胞内の位置: Virion : B1PPP0
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 129705.76

構造登録者

Williams, S.P.,Kahler, K.M.,Shotwell, J.B. (登録日: 2013-05-01, 公開日: 2013-05-29, 最終更新日: 2024-03-13)

主引用文献

Maynard, A.,Crosby, R.M.,Ellis, B.,Hamatake, R.,Hong, Z.,Johns, B.A.,Kahler, K.M.,Koble, C.,Leivers, A.,Leivers, M.R.,Mathis, A.,Peat, A.J.,Pouliot, J.J.,Roberts, C.D.,Samano, V.,Schmidt, R.M.,Smith, G.K.,Spaltenstein, A.,Stewart, E.L.,Thommes, P.,Turner, E.M.,Voitenleitner, C.,Walker, J.T.,Waitt, G.,Weatherhead, J.,Weaver, K.,Williams, S.,Wright, L.,Xiong, Z.Z.,Haigh, D.,Shotwell, J.B.
Discovery of a Potent Boronic Acid Derived Inhibitor of the HCV RNA-Dependent RNA Polymerase.
J.Med.Chem., 57:1902-1913, 2014

PubMed Abstract: A boronic acid moiety was found to be a critical pharmacophore for enhanced in vitro potency against wild-type hepatitis C replicons and known clinical polymorphic and resistant HCV mutant replicons. The synthesis, optimization, and structure-activity relationships associated with inhibition of HCV replication in a subgenomic replication system for a series of non-nucleoside boron-containing HCV RNA-dependent RNA polymerase (NS5B) inhibitors are described. A summary of the discovery of 3 (GSK5852), a molecule which entered clinical trials in subjects infected with HCV in 2011, is included.

PubMed: 23672667
DOI: 10.1021/jm400317w

実験手法

X-RAY DIFFRACTION (2.45 Å)