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GS-9669: a novel non-nucleoside inhibitor of viral polymerase for the treatment of hepatitis C virus infection.
Gentile I, Buonomo AR, Zappulo E, Coppola N, Borgia G. Gentile I, et al. Expert Rev Anti Infect Ther. 2014 Oct;12(10):1179-86. doi: 10.1586/14787210.2014.945432. Epub 2014 Aug 5. Expert Rev Anti Infect Ther. 2014. PMID: 25096404 Review.
This review focuses on the mechanism of action, pharmacokinetics, efficacy, safety and resistance of GS-9669, a non-nucleoside inhibitor of viral polymerase, active against HCV genotype 1. ...In conclusion, GS-9669 is a good candidate to be used in int …
This review focuses on the mechanism of action, pharmacokinetics, efficacy, safety and resistance of GS-9669, a non-nucleoside …
Insight into the drug resistance mechanisms of GS-9669 caused by mutations of HCV NS5B polymerase via molecular simulation.
Han D, Wang H, Wujieti B, Zhang B, Cui W, Chen BZ. Han D, et al. Comput Struct Biotechnol J. 2021 Apr 20;19:2761-2774. doi: 10.1016/j.csbj.2021.04.026. eCollection 2021. Comput Struct Biotechnol J. 2021. PMID: 34093991 Free PMC article.
GS-9669 is a non-nucleos(t)ide inhibitor (NNI) binding to the thumb site II of the Hepatitis C virus (HCV) NS5B polymerase and has advanced into phase II trials. ...Moreover, the ASMD calculations show that GS-9669 binds to the thumb II sites of the se …
GS-9669 is a non-nucleos(t)ide inhibitor (NNI) binding to the thumb site II of the Hepatitis C virus (HCV) NS5B polymerase and …
Clinical and in vitro resistance to GS-9669, a thumb site II nonnucleoside inhibitor of the hepatitis C virus NS5B polymerase.
Dvory-Sobol H, Voitenleitner C, Mabery E, Skurnac T, Lawitz EJ, McHutchison J, Svarovskaia ES, Delaney W, Miller MD, Mo H. Dvory-Sobol H, et al. Antimicrob Agents Chemother. 2014 Nov;58(11):6599-606. doi: 10.1128/AAC.02815-14. Epub 2014 Aug 25. Antimicrob Agents Chemother. 2014. PMID: 25155588 Free PMC article. Clinical Trial.
An in vitro resistance selection study with GS-9669 revealed substitutions at several NS5B residues that conferred resistance. ...Phenotypic analyses demonstrated that the viral isolates with multiple GS-9669 resistance-associated variants have reduced …
An in vitro resistance selection study with GS-9669 revealed substitutions at several NS5B residues that conferred resistance. …
Preclinical characterization of GS-9669, a thumb site II inhibitor of the hepatitis C virus NS5B polymerase.
Fenaux M, Eng S, Leavitt SA, Lee YJ, Mabery EM, Tian Y, Byun D, Canales E, Clarke MO, Doerffler E, Lazerwith SE, Lew W, Liu Q, Mertzman M, Morganelli P, Xu L, Ye H, Zhang J, Matles M, Murray BP, Mwangi J, Zhang J, Hashash A, Krawczyk SH, Bidgood AM, Appleby TC, Watkins WJ. Fenaux M, et al. Antimicrob Agents Chemother. 2013 Feb;57(2):804-10. doi: 10.1128/AAC.02052-12. Epub 2012 Nov 26. Antimicrob Agents Chemother. 2013. PMID: 23183437 Free PMC article. Clinical Trial.
GS-9669 is a highly optimized thumb site II nonnucleoside inhibitor of the hepatitis C virus (HCV) RNA polymerase, with a binding affinity of 1.35 nM for the genotype (GT) 1b protein. ...The M423T mutation is readily generated clinically upon monotherapy with the th …
GS-9669 is a highly optimized thumb site II nonnucleoside inhibitor of the hepatitis C virus (HCV) RNA polymerase, with a bind …
Efficacy of nucleotide polymerase inhibitor sofosbuvir plus the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 against HCV genotype 1 infection.
Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Subramanian GM, Symonds WT, McHutchison JG, Pang PS. Gane EJ, et al. Gastroenterology. 2014 Mar;146(3):736-743.e1. doi: 10.1053/j.gastro.2013.11.007. Epub 2013 Nov 18. Gastroenterology. 2014. PMID: 24262278 Clinical Trial.
BACKGROUND & AIMS: We evaluated an all-oral regimen comprising the nucleotide polymerase inhibitor sofosbuvir (SOF) with the NS5A inhibitor ledipasvir (LDV) or the NS5B non-nucleoside inhibitor GS-9669 in patients with genotype 1 hepatitis C virus (HCV) infectio …
BACKGROUND & AIMS: We evaluated an all-oral regimen comprising the nucleotide polymerase inhibitor sofosbuvir (SOF) with the NS5A inhibi …
Discovery of GS-9669, a thumb site II non-nucleoside inhibitor of NS5B for the treatment of genotype 1 chronic hepatitis C infection.
Lazerwith SE, Lew W, Zhang J, Morganelli P, Liu Q, Canales E, Clarke MO, Doerffler E, Byun D, Mertzman M, Ye H, Chong L, Xu L, Appleby T, Chen X, Fenaux M, Hashash A, Leavitt SA, Mabery E, Matles M, Mwangi JW, Tian Y, Lee YJ, Zhang J, Zhu C, Murray BP, Watkins WJ. Lazerwith SE, et al. J Med Chem. 2014 Mar 13;57(5):1893-901. doi: 10.1021/jm401420j. Epub 2013 Nov 6. J Med Chem. 2014. PMID: 24144213
Intrinsic potency was further improved through enantiospecific introduction of an olefin in the N-acyl motif, resulting in the discovery of the phase 2 clinical candidate GS-9669. The unexpected activity of this compound against the clinically relevant NS5B M423T mu …
Intrinsic potency was further improved through enantiospecific introduction of an olefin in the N-acyl motif, resulting in the discovery of …
Ledipasvir/sofosbuvir-based treatment of patients with chronic genotype-1 HCV infection and cirrhosis: results from two Phase II studies.
Lawitz E, Poordad F, Hyland RH, Wang J, Liu L, Dvory-Sobol H, Brainard DM, McHutchison JG, Gutierrez JA. Lawitz E, et al. Antivir Ther. 2016;21(8):679-687. doi: 10.3851/IMP3062. Epub 2016 Jun 27. Antivir Ther. 2016. PMID: 27348483 Clinical Trial.
The Phase II TRILOGY-1 and TRILOGY-2 studies investigated whether ledipasvir/sofosbuvir plus the non-nucleotide NS5B inhibitor GS-9669 or the NS3/4A protease inhibitor vedroprevir could reduce treatment duration and/or eliminate the need for ribavirin in genotype-1 …
The Phase II TRILOGY-1 and TRILOGY-2 studies investigated whether ledipasvir/sofosbuvir plus the non-nucleotide NS5B inhibitor GS- …
Utility of hepatitis C viral load monitoring on direct-acting antiviral therapy.
Sidharthan S, Kohli A, Sims Z, Nelson A, Osinusi A, Masur H, Kottilil S. Sidharthan S, et al. Clin Infect Dis. 2015 Jun 15;60(12):1743-51. doi: 10.1093/cid/civ170. Epub 2015 Mar 2. Clin Infect Dis. 2015. PMID: 25733369 Free PMC article. Clinical Trial.
METHODS: HCV genotype 1-infected, treatment-naive patients were treated with sofosbuvir and ribavirin for 24 weeks (n = 55), sofosbuvir and ledipasvir for 12 weeks (n = 20), sofosbuvir, ledipasvir, and GS-9669 for 6 weeks (n = 20), or sofosbuvir, ledipasvir, and …
METHODS: HCV genotype 1-infected, treatment-naive patients were treated with sofosbuvir and ribavirin for 24 weeks (n = 55), sofosbuvir and …
The paradox of highly effective sofosbuvir-based combination therapy despite slow viral decline: can we still rely on viral kinetics?
Nguyen THT, Guedj J, Uprichard SL, Kohli A, Kottilil S, Perelson AS. Nguyen THT, et al. Sci Rep. 2017 Aug 31;7(1):10233. doi: 10.1038/s41598-017-09776-z. Sci Rep. 2017. PMID: 28860456 Free PMC article. Clinical Trial.
High sustained virologic response (SVR) rates have been observed after 6 weeks of anti-HCV treatment using sofosbuvir, ledipasvir and a non-nucleoside polymerase-inhibitor (GS-9669) or a protease-inhibitor (GS-9451) and after 12 weeks with sofosbuvir + ledipa …
High sustained virologic response (SVR) rates have been observed after 6 weeks of anti-HCV treatment using sofosbuvir, ledipasvir and a non- …
20 results