ArticleAntimicrobial agents and chemotherapy2009
In vitro activity and preclinical profile of TMC435350, a potent hepatitis C virus protease inhibitor.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
63 citing papers in PubMed, 190 citations in OpenAlex.
- Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naïve genotype 1 hepatitis C: the randomized PILLAR study.Hepatology (Baltimore, Md.) · 2013Trial
- Unraveling the therapeutic landscape of approved non-peptide macrocycles.Acta pharmaceutica Sinica. B · 2025Review
- Polymorphic Structure Determination of the Macrocyclic Drug Paritaprevir by MicroED.Advanced biology · 2024Article
- Computer-Aided Prediction of the Interactions of Viral Proteases with Antiviral Drugs: Antiviral Potential of Broad-Spectrum Drugs.Molecules (Basel, Switzerland) · 2023Article
- Polymorphic Structure Determination of the Macrocyclic Drug Paritaprevir by MicroED.bioRxiv : the preprint server for biology · 2023Article
- The Impact of interferon lambda 3 Polymorphism on Hepato-Cellular Carcinoma Progression in Hepatitis C Virus Patients: Treatment-Naïve and Experienced.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- Viral proteases as therapeutic targets.Molecular aspects of medicine · 2022Review
- Progress, evolving therapeutic/diagnostic approaches, and challenges in the management of hepatitis C virus infections.Archives of virology · 2022Review
- Hepatitis C Virus Protease Inhibitors Show Differential Efficacy and Interactions with Remdesivir for Treatment of SARS-CoV-2Antimicrobial agents and chemotherapy · 2021Article
- Simeprevir Potently Suppresses SARS-CoV-2 Replication and Synergizes with Remdesivir.ACS central science · 2021Article
- In vitro susceptibility of humanSaudi journal of biological sciences · 2021Article
- Design and Synthesis of Novel Symmetric Fluorene-2,7-Diamine Derivatives as Potent Hepatitis C Virus Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Isocotoin suppresses hepatitis E virus replication through inhibition of heat shock protein 90.Antiviral research · 2021Article
- Preclinical evaluation of Amphihevir, a first-in-class clinical Hepatitis C virus NS4B inhibitor.Antimicrobial agents and chemotherapy · 2019Article
- GII.4 Norovirus Protease Shows pH-Sensitive Proteolysis with a Unique Arg-His Pairing in the Catalytic Site.Journal of virology · 2019Article
- Resistance outside the substrate envelope: hepatitis C NS3/4A protease inhibitors.Critical reviews in biochemistry and molecular biology · 2019Review
- Effect of Plasma Protein Binding on the Anti-Hepatitis B Virus Activity and Pharmacokinetic Properties of NVR 3-778.Antimicrobial agents and chemotherapy · 2018Article
- GP205, a new hepatitis C virus NS3/4A protease inhibitor, displays higher metabolic stability in vitro and drug exposure in vivo.Acta pharmacologica Sinica · 2018Article
- Current therapy for chronic hepatitis C: The role of direct-acting antivirals.Antiviral research · 2017Review
- Efficient Hepatitis C Virus Genotype 1b Core-NS5A Recombinants Permit Efficacy Testing of Protease and NS5A Inhibitors.Antimicrobial agents and chemotherapy · 2017Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hepatitis C virus (HCV) NS3/4A serine protease has been explored as a target for the inhibition of viral replication in preclinical models and in HCV-infected patients. TMC435350 is a highly specific and potent inhibitor of NS3/4A protease selected from a series of novel macrocyclic inhibitors. In biochemical assays using NS3/4A proteases of genotypes 1a and 1b, inhibition constants of 0.5 and 0.4 nM, respectively, were determined. TMC435350 inhibited HCV replication in a cellular assay (subgenomic 1b replicon) with a half-maximal effective concentration (EC(50)) of 8 nM and a selectivity index of 5,875. The compound was synergistic with alpha interferon and an NS5B inhibitor in the replicon model and additive with ribavirin. In rats, TMC435350 was extensively distributed to the liver and intestinal tract (tissue/plasma area under the concentration-time curve ratios of >35), and the absolute bioavailability was 44% after a single oral administration. Compound concentrations detected in both plasma and liver at 8 h postdosing were above the EC(99) value measured in the replicon. In conclusion, given the selective and potent in vitro anti-HCV activity, the potential for combination with other anti-HCV agents, and the favorable pharmacokinetic profile, TMC435350 has been selected for clinical development.
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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.