Structure-Based Design of a Benzodiazepine Scaffold Yields a Potent Allosteric Inhibitor of Hepatitis C NS5B RNA Polymerase
Copyright policy )Structure-Based Design of a Benzodiazepine Scaffold Yields a Potent Allosteric Inhibitor of Hepatitis C NS5B RNA Polymerase
HCV NS5B polymerase, an essential and virus-specific enzyme, is an important target for drug discovery. Using structure-based design, we optimized a 1,5-benzodiazepine NS5B polymerase inhibitor chemotype into a new sulfone-containing scaffold. The design yielded potent inhibitor (S)-4c (K(D) = 0.79 nM), which has approximately 20-fold greater affinity for NS5B than its carbonyl analogue (R)-2c.
- Johnson & Johnson (United States) United States
- Tibotec United States
- Johnson & Johnson Pharmaceutical Research and Development China (People's Republic of)
Models, Molecular, Benzodiazepines, Allosteric Regulation, Drug Design, Molecular Conformation, Hepacivirus, Enzyme Inhibitors, Viral Nonstructural Proteins, Crystallography, X-Ray, RNA-Dependent RNA Polymerase
Models, Molecular, Benzodiazepines, Allosteric Regulation, Drug Design, Molecular Conformation, Hepacivirus, Enzyme Inhibitors, Viral Nonstructural Proteins, Crystallography, X-Ray, RNA-Dependent RNA Polymerase
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