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PDBsum entry 2qe5
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References listed in PDB file
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Key reference
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Title
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Identification of anthranilic acid derivatives as a novel class of allosteric inhibitors of hepatitis c ns5b polymerase.
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Authors
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T.Nittoli,
K.Curran,
S.Insaf,
M.Digrandi,
M.Orlowski,
R.Chopra,
A.Agarwal,
A.Y.Howe,
A.Prashad,
M.B.Floyd,
B.Johnson,
A.Sutherland,
K.Wheless,
B.Feld,
J.O'Connell,
T.S.Mansour,
J.Bloom.
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Ref.
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J Med Chem, 2007,
50,
2108-2116.
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PubMed id
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Abstract
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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.
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