3h2l

Crystal structure of HCV NS5B polymerase in complex with a novel bicyclic dihydro-pyridinone inhibitorCrystal structure of HCV NS5B polymerase in complex with a novel bicyclic dihydro-pyridinone inhibitor

Structural highlights 3h2l is a 2 chain structure with sequence from Viruses. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Activity: RNA-directed RNA polymerase, with EC number 2.7.7.48 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed A novel series of non-nucleoside small molecules containing a tricyclic dihydropyridinone structural motif was identified as potent HCV NS5B polymerase inhibitors. Driven by structure-based design and building on our previous efforts in related series of molecules, we undertook extensive SAR studies, in which we identified a number of metabolically stable and very potent compounds in genotype 1a and 1b replicon assays. This work culminated in the discovery of several inhibitors, which combined potent in vitro antiviral activity against both 1a and 1b genotypes, metabolic stability, good oral bioavailability, and high C(12) (PO)/EC(50) ratios. Discovery of tricyclic 5,6-dihydro-1H-pyridin-2-ones as novel, potent, and orally bioavailable inhibitors of HCV NS5B polymerase.,Ruebsam F, Murphy DE, Tran CV, Li LS, Zhao J, Dragovich PS, McGuire HM, Xiang AX, Sun Z, Ayida BK, Blazel JK, Kim SH, Zhou Y, Han Q, Kissinger CR, Webber SE, Showalter RE, Shah AM, Tsan M, Patel RA, Thompson PA, Lebrun LA, Hou HJ, Kamran R, Sergeeva MV, Bartkowski DM, Nolan TG, Norris DA, Khandurina J, Brooks J, Okamoto E, Kirkovsky L Bioorg Med Chem Lett. 2009 Nov 15;19(22):6404-12. Epub 2009 Sep 17. PMID:19818610 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also RNA polymerase

spinqualitylabelsall models 3h2l, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image