4KHM

HCV NS5B GT1A with GSK5852

Summary for 4KHM

• Entry DOI: 10.2210/pdb4khm/pdb
• Related: 4KAI 4KB7 4KBI 4KE5 4KHR
• Descriptor: HCV Polymerase, [4-({[5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-6-yl](methylsulfonyl)amino}methyl)-2-fluorophenyl]boronic acid, SULFATE ION, ... (4 entities in total)
• Functional Keywords: hcv polymerase, hcv ns5b, site iv inhibitor, boron, p66, p70, rna dependent rna polymerase, rna directed rna polymerase, replication-replication inhibitor complex, replication/replication inhibitor
• Biological source: Hepatitis C virus subtype 1a (HCV)
• Total number of polymer chains: 2
• Total formula weight: 129851.88

Authors

Williams, S.P.,Kahler, K.M.,Shotwell, J.B. (deposition date: 2013-04-30, release date: 2013-05-15, Last modification date: 2024-03-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.7 Å)