title: Discovery of GS-9256: a novel phosphinic acid derived inhibitor of the hepatitis C virus NS3/4A protease with potent clinical activity.
abstract: A potent and novel class of phosphinic acid derived product-like inhibitors of the HCV NS3/4A protease was discovered previously. Modification of the phosphinic acid and quinoline heterocycle led to GS-9256 with potent cell-based activity and favorable pharmacokinetic parameters. Based on these attributes, GS-9256 was advanced to human clinical trial as a treatment for chronic infection with genotype 1 HCV.
authors.affiliation: Gilead Sciences, Inc., 333 Lakeside Dr, Foster City, CA 94404, USA. csheng@gilead.com
authors.forename: X Christopher
authors.initials: XC
authors.lastname: Sheng
authors.forename: Anthony
authors.initials: A
authors.lastname: Casarez
authors.forename: Ruby
authors.initials: R
authors.lastname: Cai
authors.forename: Michael O
authors.initials: MO
authors.lastname: Clarke
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Chen
authors.forename: Aesop
authors.initials: A
authors.lastname: Cho
authors.forename: William E
authors.initials: WE
authors.lastname: Delaney
authors.forename: Edward
authors.initials: E
authors.lastname: Doerffler
authors.forename: Mingzhe
authors.initials: M
authors.lastname: Ji
authors.forename: Michael
authors.initials: M
authors.lastname: Mertzman
authors.forename: Rowchanak
authors.initials: R
authors.lastname: Pakdaman
authors.forename: Hyung-Jung
authors.initials: HJ
authors.lastname: Pyun
authors.forename: Tanisha
authors.initials: T
authors.lastname: Rowe
authors.forename: Qiaoyin
authors.initials: Q
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Choung U
authors.initials: CU
authors.lastname: Kim
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D004285:Dogs; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D020128:Inhibitory Concentration 50; D047908:Intracellular Signaling Peptides and Proteins; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010721:Phosphinic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013552:Swine; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D010456:Peptides, Cyclic; D010721:Phosphinic Acids; D017361:Viral Nonstructural Proteins; C571665:GS-9256; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus