Fragment-based discovery of hepatitis C virus NS5b RNA polymerase inhibitors
Journal Article
·
· Bioorg. Med. Chem. Lett.
- SGX
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 {approx}1-10 mM binding affinity (K{sub D}) were iteratively optimized to give leads with {approx}200 nM biochemical activity and low {micro}M cellular activity in a Replicon assay.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1007119
- Journal Information:
- Bioorg. Med. Chem. Lett., Vol. 18, Issue (9) ; 05, 2008; ISSN 0960-894X
- Country of Publication:
- United States
- Language:
- ENGLISH
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