Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1376581 | Bioorganic & Medicinal Chemistry Letters | 2008 | 6 Pages |
Abstract
Non-nucleoside inhibitors of HCV NS5b RNA polymerase were discovered by a fragment-based lead discovery approach, beginning with crystallographic fragment screening. The NS5b binding affinity and biochemical activity of fragment hits and inhibitors was determined by surface plasmon resonance (Biacore) and an enzyme inhibition assay, respectively. Crystallographic fragment screening hits with ∼1–10 mM binding affinity (KD) were iteratively optimized to give leads with ∼200 nM biochemical activity and low μM cellular activity in a Replicon assay.
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Authors
Stephen S. Antonysamy, Brandon Aubol, Jeff Blaney, Michelle F. Browner, Anthony M. Giannetti, Seth F. Harris, Normand Hébert, Jörg Hendle, Stephanie Hopkins, Elizabeth Jefferson, Charles Kissinger, Vincent Leveque, David Marciano, Ethel McGee,