Trial reportAntimicrobial agents and chemotherapy2013
Preclinical characterization of GS-9669, a thumb site II inhibitor of the hepatitis C virus NS5B polymerase.
Trial report in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01431898 (A Phase 1b, Randomized, Single-Blind, Multiple-Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-9669 in Subjects With Chronic Hepatitis C Virus Infection), which is not on this map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1b, Randomized, Single-Blind, Multiple-Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-9669 in Subjects With Chronic Hepatitis C Virus Infection
Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- Genotypic and phenotypic analyses of hepatitis C virus variants observed in clinical studies of VX-222, a nonnucleoside NS5B polymerase inhibitor.Antimicrobial agents and chemotherapy · 2014Trial
- Discovery of non-nucleoside inhibitors of the enterovirus D68 3D polymerase through crystallographic fragment and high-throughput biochemical screening.bioRxiv : the preprint server for biology · 2026Article
- Crystallographic Fragment Screening of the Dengue Virus Polymerase Reveals Multiple Binding Sites for the Development of Non-nucleoside Antiflavivirals.Journal of medicinal chemistry · 2025Article
- RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic.European journal of medicinal chemistry · 2021Review
- Insight into the drug resistance mechanisms of GS-9669 caused by mutations of HCV NS5B polymerase via molecular simulation.Computational and structural biotechnology journal · 2021Article
- Biophysical Mode-of-Action and Selectivity Analysis of Allosteric Inhibitors of Hepatitis C Virus (HCV) Polymerase.Viruses · 2017Article
- Current therapy for chronic hepatitis C: The role of direct-acting antivirals.Antiviral research · 2017Review
- PTC725, an NS4B-Targeting Compound, Inhibits a Hepatitis C Virus Genotype 3 Replicon, as Predicted by Genome Sequence Analysis and Determined Experimentally.Antimicrobial agents and chemotherapy · 2016Article
- Antiviral Nucleotide Incorporation by Recombinant Human Mitochondrial RNA Polymerase Is Predictive of Increased In Vivo Mitochondrial Toxicity Risk.Antimicrobial agents and chemotherapy · 2016Article
- Review
- In vitro activity and resistance profile of dasabuvir, a nonnucleoside hepatitis C virus polymerase inhibitor.Antimicrobial agents and chemotherapy · 2015Article
- Cross-genotypic examination of hepatitis C virus polymerase inhibitors reveals a novel mechanism of action for thumb binders.Antimicrobial agents and chemotherapy · 2014Article
- Clinical and in vitro resistance to GS-9669, a thumb site II nonnucleoside inhibitor of the hepatitis C virus NS5B polymerase.Antimicrobial agents and chemotherapy · 2014Article
- Inhibitors of the tick-borne, hemorrhagic fever-associated flaviviruses.Antimicrobial agents and chemotherapy · 2014Article
- Robust and persistent replication of the genotype 6a hepatitis C virus replicon in cell culture.Antimicrobial agents and chemotherapy · 2014Article
- Hepatitis C virus genetic variability and the presence of NS5B resistance-associated mutations as natural polymorphisms in selected genotypes could affect the response to NS5B inhibitors.Antimicrobial agents and chemotherapy · 2014Article
- Article
- Inhibition of hepatitis C virus replication by GS-6620, a potent C-nucleoside monophosphate prodrug.Antimicrobial agents and chemotherapy · 2014Article
- Preclinical characterization of the novel hepatitis C virus NS3 protease inhibitor GS-9451.Antimicrobial agents and chemotherapy · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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. It is a selective inhibitor of HCV RNA replication, with a mean 50% effective concentration (EC(50)) of ≤ 11 nM in genotype 1 and 5 replicon assays, but lacks useful activity against genotypes 2 to 4. The M423T mutation is readily generated clinically upon monotherapy with the thumb site II inhibitors filibuvir and lomibuvir, and it is notable that GS-9669 exhibited only a 3-fold loss in potency against this variant in the genotype 1b replicon. Rather than M423T, resistance predominantly tracks to residues R422K and L419M and residue I482L in GT 1b and 1a replicons, respectively. GS-9669 exhibited at least additive activity in combination with agents encompassing four other direct modes of action (NS3 protease, NS5A, NS5B via an alternative allosteric binding site, and NS5B nucleotide) as well as with alpha interferon or ribavirin in replicon assays. It exhibited high metabolic stability in in vitro human liver microsomal assays, which, in combination with its pharmacokinetic profiles in rat, dog, and two monkey species, is predictive of good human pharmacokinetics. GS-9669 is well suited for combination with other orally active, direct-acting antiviral agents in the treatment of genotype 1 chronic HCV infection. (This study has been registered at ClinicalTrials.gov under registration number NCT01431898.).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.