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Publication and contact information

Infectious disease


HCV NS3/4A protein complex

Fragment-based screening using crystals of the HCV NS3/4A holoenzyme identified inhibitors of an allosteric site that could help treat HCV infection. Structure-guided optimization of a lead fragment against an allosteric site on the HCV NS3/4A holoenzyme yielded a compound that inhibited the enzyme with an IC50 under 10 nM. In a cell-based assay, the optimized compound showed antiviral activity with an EC50 of 8.3 nM. IND-enabling studies of an optimized molecule that binds the same site are ongoing.
Astex Pharmaceuticals Inc.'s lead HCV NS3/4A protease inhibitor, which is the optimized molecule, is in preclinical development to treat HCV infection.
Vertex Pharmaceuticals Inc. markets Incivek telaprevir, a small molecule HCV NS3/4A protease inhibitor, to treat HCV infection.
Merck & Co. Inc. markets Victrelis boceprevir, a small molecule HCV NS3/4A protease inhibitor, for the same indication.
At least six other companies have inhibitors of the HCV NS3/4A protease in Phase III testing or earlier to treat HCV infection (see Closing time for HCV protease, page 6).

SciBX 5(40); doi:10.1038/scibx.2012.1055
Published online Oct. 11, 2012

Patent applications filed covering composition of matter; available for licensing and partnering

Saalau-Bethell, S.M. et al. Nat. Chem. Biol.; published online Sept. 30, 2012;
Contact: Harren Jhoti,
Astex Pharmaceuticals Inc., Cambridge, U.K.