4TN2

NS5b in complex with lactam-thiophene carboxylic acids

Summary for 4TN2

Entry DOI	10.2210/pdb4tn2/pdb
Descriptor	Genome polyprotein, 3-[(2R)-2-cyclohexyl-5-oxopyrrolidin-1-yl]-5-phenylthiophene-2-carboxylic acid (3 entities in total)
Functional Keywords	complex polymerase inhbitor, hydrolase
Biological source	Hepatitis B virus (isolate BK, HCV)
Total number of polymer chains	1
Total formula weight	64558.98
Authors	Chopra, R. (deposition date: 2014-06-02, release date: 2014-09-17, Last modification date: 2023-12-27)
Primary citation	Barnes-Seeman, D.,Boiselle, C.,Capacci-Daniel, C.,Chopra, R.,Hoffmaster, K.,Jones, C.T.,Kato, M.,Lin, K.,Ma, S.,Pan, G.,Shu, L.,Wang, J.,Whiteman, L.,Xu, M.,Zheng, R.,Fu, J. Design and synthesis of lactam-thiophene carboxylic acids as potent hepatitis C virus polymerase inhibitors. Bioorg.Med.Chem.Lett., 24:3979-3985, 2014 Cited by PubMed Abstract: Herein we report the successful incorporation of a lactam as an amide replacement in the design of hepatitis C virus NS5B Site II thiophene carboxylic acid inhibitors. Optimizing potency in a replicon assay and minimizing potential risk for CYP3A4 induction led to the discovery of inhibitor 22a. This lead compound has a favorable pharmacokinetic profile in rats and dogs. PubMed: 24986660 DOI: 10.1016/j.bmcl.2014.06.031 PDB entries with the same primary citation
Experimental method	X-RAY DIFFRACTION (2.7 Å)

Structure validation