3CWJ

Crystal structure of hcv ns5b polymerase with a novel pyridazinone inhibitor

Summary for 3CWJ

• Entry DOI: 10.2210/pdb3cwj/pdb
• Related: 3BR9 3BSA 3BSC 3CDE 3CO9 3CVK
• Descriptor: RNA-DIRECTED RNA POLYMERASE, N-{3-[5-hydroxy-2-(3-methylbutyl)-3-oxo-6-thiophen-2-yl-2,3-dihydropyridazin-4-yl]-1,1-dioxido-2H-1,4-benzothiazin-7-yl}methanesulfonamide (3 entities in total)
• Functional Keywords: protein-ligand complex, rna replication, rna-binding, rna-directed rna polymerase, hepatitis, transferase, viral protein
• Biological source: Hepatitis C virus
• Total number of polymer chains: 2
• Total formula weight: 129764.76

Authors

Han, Q.,Showalter, R.E.,Zhao, Q.,Kissinger, C.R. (deposition date: 2008-04-21, release date: 2009-04-21, Last modification date: 2024-10-30)

Primary citation

Ellis, D.A.,Blazel, J.K.,Webber, S.E.,Tran, C.V.,Dragovich, P.S.,Sun, Z.,Ruebsam, F.,McGuire, H.M.,Xiang, A.X.,Zhao, J.,Li, L.S.,Zhou, Y.,Han, Q.,Kissinger, C.R.,Showalter, R.E.,Lardy, M.,Shah, A.M.,Tsan, M.,Patel, R.,LeBrun, L.A.,Kamran, R.,Bartkowski, D.M.,Nolan, T.G.,Norris, D.A.,Sergeeva, M.V.,Kirkovsky, L.
4-(1,1-Dioxo-1,4-dihydro-1lambda6-benzo[1,4]thiazin-3-yl)-5-hydroxy-2H-pyridazin-3-ones as potent inhibitors of HCV NS5B polymerase
Bioorg.Med.Chem.Lett., 18:4628-4632, 2008

PubMed Abstract: 4-(1,1-Dioxo-1,4-dihydro-1lambda(6)-benzo[1,4]thiazin-3-yl)-5-hydroxy-2H-pyridazin-3-one analogs were discovered as a novel class of inhibitors of HCV NS5B polymerase. Structure-based design led to the identification of compound 3a that displayed potent inhibitory activities in biochemical and replicon assays (1b IC(50)<10 nM; 1b EC(50)=1.1 nM) as well as good stability toward human liver microsomes (HLM t(1/2)>60 min).

PubMed: 18662878
DOI: 10.1016/j.bmcl.2008.07.014

Experimental method

X-RAY DIFFRACTION (2.4 Å)