4MKB: Hepatitis C Virus Polymerase Ns5b Genotype 1b (bk) In Complex With Inhibitor 14 (n-(4-{(e)-2-[3-tert-butyl-2-methoxy-5-(3-oxo-2,3- Dihydropyridazin-4-yl)phenyl]ethenyl}phenyl)methanesulfonamide)

Hepatitis C virus (HCV) is a major global public health problem. While the current standard of care, a direct-acting antiviral (DAA) protease inhibitor taken in combination with pegylated interferon and ribavirin, represents a major advancement in recent years, an unmet medical need still exists for treatment modalities that improve upon both efficacy and tolerability. Toward those ends, much effort has continued to focus on the discovery of new DAAs, with the ultimate goal to provide interferon-free combinations. The RNA-dependent RNA polymerase enzyme NS5B represents one such DAA therapeutic target for inhibition that has attracted much interest over the past decade. Herein, we report the discovery and optimization of a novel series of inhibitors of HCV NS5B, through the use of structure-based design applied to a fragment-derived starting point. Issues of potency, pharmacokinetics, and early safety were addressed in order to provide a clinical candidate in fluoropyridone 19.
PDB ID: 4MKBDownload
MMDB ID: 114243
PDB Deposition Date: 2013/9/4
Updated in MMDB: 2013/10
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Source Organism:
Similar Structures:
Biological Unit for 4MKB: monomeric; determined by author and by software (PISA)
Molecular Components in 4MKB
Label Count Molecule
Protein (1 molecule)
RNA-directed RNA Polymerase
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB