Results 181 to 190 of about 15,799 (221)

Discovery of an irreversible HCV NS5B polymerase inhibitor

Bioorganic & Medicinal Chemistry Letters, 2013
The discovery of lead compound 2e was described. Its covalent binding to HCV NS5B polymerase enzyme was investigated by X-ray analysis. The results of distribution, metabolism and pharmacokinetics were reported. Compound 2e was demonstrated to be potent (replicon GT-1b EC50 = 0.003 μM), highly selective, and safe in in vitro and in vivo assays.
Qingbei, Zeng, Anilkumar G, Nair, Stuart B, Rosenblum, Hsueh-Cheng, Huang, Charles A, Lesburg, Yueheng, Jiang, Oleg, Selyutin, Tin-Yau, Chan, Frank, Bennett, Kevin X, Chen, Srikanth, Venkatraman, Mousumi, Sannigrahi, Francisco, Velazquez, Jose S, Duca, Stephen, Gavalas, Yuhua, Huang, Haiyan, Pu, Li, Wang, Patrick, Pinto, Bancha, Vibulbhan, Sony, Agrawal, Eric, Ferrari, Chuan-kui, Jiang, Cheng, Li, David, Hesk, Jennifer, Gesell, Steve, Sorota, Neng-Yang, Shih, F George, Njoroge, Joseph A, Kozlowski   +29 more
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The HCV NS5B Nucleoside and Non-Nucleoside Inhibitors

Clinics in Liver Disease, 2011
This article introduces one of the most diverse classes of direct-acting antivirals for hepatitis C, the nucleoside and non-nucleoside NS5B polymerase inhibitors. Through a systematic review of the published literature, we describe their structure, mechanism of action, issues with resistance, and clinical effectiveness shown in the latest clinical ...
Fernando E, Membreno, Eric J, Lawitz
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HCV NS5B polymerase inhibitors.

Current opinion in drug discovery & development, 2010
In the past decade, intensive efforts have focused on the discovery of both nucleos(t)ide and non-nucleoside inhibitors of the HCV NS5B polymerase. These efforts have resulted in several promising agents advancing in clinical development. This review traces the history of optimization of the chemical series that have led to the development of clinical ...
William J, Watkins, Adrian S, Ray, Lee S, Chong   +2 more
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Tetracyclic indole inhibitors of hepatitis C virus NS5B-polymerase

Bioorganic & Medicinal Chemistry Letters, 2009
We report the evolutionary path from an open-chain series to conformationally constrained tetracyclic indole inhibitors of HCV NS5B-polymerase, where the C2 aromatic is tethered to the indole nitrogen. SAR studies led to the discovery of zwitterionic compounds endowed with good intrinsic enzyme affinity and cell-based potency, as well as superior DMPK ...
Ian, Stansfield, Caterina, Ercolani, Angela, Mackay, Immacolata, Conte, Marco, Pompei, Uwe, Koch, Nadia, Gennari, Claudio, Giuliano, Michael, Rowley, Frank, Narjes   +9 more
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3-Heterocyclyl quinolone inhibitors of the HCV NS5B polymerase

Bioorganic & Medicinal Chemistry Letters, 2012
The discovery and optimization of a novel class of quinolone small-molecules that inhibit NS5B polymerase, a key enzyme of the HCV viral life-cycle, is described. Our research led to the replacement of a hydrolytically labile ester functionality with bio-isosteric heterocycles.
Dange V, Kumar, Roopa, Rai, Ken A, Brameld, Jennifer, Riggs, John R, Somoza, Ravi, Rajagopalan, James W, Janc, Yu M, Xia, Tony L, Ton, Huiyong, Hu, Isabelle, Lehoux, Joseph D, Ho, Wendy B, Young, Barry, Hart, Michael J, Green   +14 more
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Hepatitis C Virus RNA-Dependent RNA Polymerase (NS5B Polymerase)

2000
Approximately 170 million people world-wide are chronically infected with the hepatitis C virus (HCV) (BRADLEY et al. 1983; CHOO et al. 1989; HOUGHTON 1996; A;LTER 1997; also see Thomas, this volume). Although chronic infection with HCV frequently produces no symptoms for 5–30 years, it eventually has adverse effects on the host and constitutes a major
C H, Hagedorn, E H, van Beers, C, De Staercke   +2 more
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A nonisotopic assay method for hepatitis C virus NS5B polymerase

Journal of Virological Methods, 2002
The RNA-dependent RNA polymerase of hepatitis C virus (HCV) is responsible for replication of genomic RNA. A novel nonisotopic assay method is described for detecting its enzymatic activity. The 5' end of the in vitro-transcribed template RNA was attached covalently to the surface of a Covalink module using carbodiimide condensation.
Chanhee, Park, Younghoon, Kee, Jungchan, Park, Heejoon, Myung   +3 more
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Hepatitis C Virus RNA-Dependent RNA Polymerase (NS5B Polymerase)

2003
The hepatitis C virus (HCV) chronically infects approx 4 million patients in the United States alone, and constitutes a major cause of chronic liver disease and hepatocellular carcinoma (1-3). Current antiviral therapies for chronic hepatitis C remain relatively ineffective and have significant side-effects in many patients.
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Molecular Modeling of HCV NS5B Inhibitors

2009
The worldwide prevalence of hepatitis C virus (HCV) infection and important health consequences associated with the chronic state of the disease, have become a serious health problem worldwide. To date, no vaccine is available to prevent this disease, and no specific antiviral agent directed against this dangerous human pathogen is at hand.
Paneni MS, POSOCCO, PAOLA, FERMEGLIA, MAURIZIO, PRICL, SABRINA   +3 more
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ARHGEF18 can promote BVDV NS5B activation of the host NF-κB signaling pathway by combining with the NS5B-palm domain

Veterinary Microbiology
Rho guanine nucleotide exchange factor 18 (ARHGEF18) is a member of the Rho guanine nucleotide exchange factor (RhoGEF) family. RhoGEF plays an important role in the occurrence of tumors and neurological diseases; however, its involvement in host cell resistance against pathogenic microorganisms is mostly unknown.
Jiying, Yin, Naichao, Diao, Tian, Tian, Qi, Wang, Shuqi, Ma, Ning, He, Hongming, Zhou, Zehui, Zhou, Wenyi, Jia, Xiaonan, Wang, Kun, Shi, Rui, Du   +11 more
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