3lox | pdb_00003lox

HCV NS3-4a protease domain with a ketoamide inhibitor derivative of Boceprevir bound

spinqualitylabelsall models 3lox, resolution 2.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3lox is a 4 chain structure with sequence from Hepatitis c virus subtype 1a. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BME, MCX, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed In the search for a second generation HCV protease inhibitor, molecular modeling studies of the X-ray crystal structure of Boceprevir1 bound to the NS3 protein suggest that expansion into the S4 pocket could provide additional hydrophobic Van der Waals interactions. Effective replacement of the P4 tert-butyl with a cyclohexylmethyl ligand led to inhibitor 2 with improved enzyme and replicon activities. Subsequent modeling and SAR studies led to the pyridine 38 and sulfone analogues 52 and 53 with vastly improved PK parameters in monkeys, forming a new foundation for further exploration. The introduction of P4 substituted 1-methylcyclohexyl groups into Boceprevir: a change in direction in the search for a second generation HCV NS3 protease inhibitor.,Bennett F, Huang Y, Hendrata S, Lovey R, Bogen SL, Pan W, Guo Z, Prongay A, Chen KX, Arasappan A, Venkatraman S, Velazquez F, Nair L, Sannigrahi M, Tong X, Pichardo J, Cheng KC, Girijavallabhan VM, Saksena AK, Njoroge FG Bioorg Med Chem Lett. 2010 Apr 15;20(8):2617-21. Epub 2010 Feb 19. PMID:20303756 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Proliferating cell nuclear antigen 3D structures

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