2QE2

Structure of HCV NS5B Bound to an Anthranilic Acid Inhibitor

Summary for 2QE2

• Entry DOI: 10.2210/pdb2qe2/pdb
• Related: 2QE5
• Descriptor: RNA-directed RNA polymerase, 2-{[N-(2-ACETYL-5-CHLORO-4-FLUOROPHENYL)GLYCYL]AMINO}BENZOIC ACID (2 entities in total)
• Functional Keywords: transferase
• Biological source: Hepatitis C virus subtype 1b
• Total number of polymer chains: 2
• Total formula weight: 129224.71

Authors

Chopra, R.,Svenson, K.,Bard, J. (deposition date: 2007-06-22, release date: 2007-10-02, Last modification date: 2024-10-30)

Primary citation

Nittoli, T.,Curran, K.,Insaf, S.,DiGrandi, M.,Orlowski, M.,Chopra, R.,Agarwal, A.,Howe, A.Y.M.,Prashad, A.,Brawner Floyd, M.,Johnson, B.,Sutherland, A.,Wheless, K.,Feld, B.,O'Connell, J.,Mansour, T.S.,Bloom, J.
Identification of Anthranilic Acid Derivatives as a Novel Class of Allosteric Inhibitors of Hepatitis C NS5B Polymerase
J.Med.Chem., 50:2108-2116, 2007

PubMed Abstract: A series of potent anthranilic acid-based inhibitors of the hepatitis C NS5B polymerase has been identified. The inhibitors bind to a site on NS5B between the thumb and palm regions adjacent to the active site as determined by X-ray crystallography of the enzyme-inhibitor complex. Guided by both molecular modeling and traditional SAR, the enzyme activity of the initial hit was improved by approximately 100-fold, yielding a series of potent and selective NS5B inhibitors with IC50 values as low as 10 nM. These compounds were also inhibitors of the HCV replicon in cultured HUH7 cells.

PubMed: 17402724
DOI: 10.1021/jm061428x

Experimental method

X-RAY DIFFRACTION (2.9 Å)