ArticleAntimicrobial agents and chemotherapy2012
Preclinical Profile and Characterization of the Hepatitis C Virus NS3 Protease Inhibitor Asunaprevir (BMS-650032).
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 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
66 citing papers in PubMed, 183 citations in OpenAlex.
- Exposure-Response (Efficacy) Analysis of Daclatasvir and Asunaprevir in Japanese Patients With Hepatitis C Virus Infection.Journal of clinical pharmacology · 2018Trial
- Daclatasvir plus asunaprevir in treatment-naïve patients with hepatitis C virus genotype 1b infection.World journal of gastroenterology · 2018Trial
- Trial
- Daclatasvir/asunaprevir/beclabuvir fixed-dose combination in Japanese patients with HCV genotype 1 infection.Journal of gastroenterology · 2017Trial
- Daclatasvir, sofosbuvir, and ribavirin for hepatitis C virus genotype 3 and advanced liver disease: A randomized phase III study (ALLY-3+).Hepatology (Baltimore, Md.) · 2016Trial
- In vitro and in vivo antiviral activity and resistance profile of the hepatitis C virus NS3/4A protease inhibitor ABT-450.Antimicrobial agents and chemotherapy · 2015Trial
- The pharmacokinetics of daclatasvir and asunaprevir administered in combination in studies in healthy subjects and patients infected with hepatitis C virus.Clinical drug investigation · 2014Trial
- Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection.Hepatology (Baltimore, Md.) · 2014Trial
- Article
- Degron tagging for rapid protein degradation in mice.Disease models & mechanisms · 2024Article
- Therapeutic Intervention of Serine Protease Inhibitors against Hepatitis C Virus.Current medicinal chemistry · 2024Article
- Endosome-microautophagy targeting chimera (eMIATAC) for targeted proteins degradation and enhance CAR-T cell anti-tumor therapy.Theranostics · 2024Article
- The Role of CYPs and Transporters in the Biotransformation and Transport of the Anti-hepatitis C Antiviral Agents Asunaprevir, Daclatasvir, and Beclabuvir: Impact of Liver Disease, Race and Drug-drug Interactions on Safety and Efficacy.Current drug metabolism · 2024Review
- Use of In Vivo Imaging and Physiologically-Based Kinetic Modelling to Predict Hepatic Transporter Mediated Drug-Drug Interactions in Rats.Pharmaceutics · 2023Article
- In silico prediction of SARS-CoV-2 main protease and polymerase inhibitors: 3D-Pharmacophore modelling.Journal of biomolecular structure & dynamics · 2022Article
- Real-world long-term analysis of daclatasvir plus asunaprevir in patients with hepatitis C virus infection.JGH open : an open access journal of gastroenterology and hepatology · 2022Article
- On the cutting edge: protease-based methods for sensing and controlling cell biology.Nature methods · 2020Review
- Modulation of chimeric antigen receptor surface expression by a small molecule switch.BMC biotechnology · 2019Article
- Precisely controlling endogenous protein dosage in hPSCs and derivatives to model FOXG1 syndrome.Nature communications · 2019Article
- Hepatitis C virus cell culture models: an encomium on basic research paving the road to therapy development.Medical microbiology and immunology · 2019Review
6 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
19 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Asunaprevir (ASV; BMS-650032) is a hepatitis C virus (HCV) NS3 protease inhibitor that has demonstrated efficacy in patients chronically infected with HCV genotype 1 when combined with alfa interferon and/or the NS5A replication complex inhibitor daclatasvir. ASV competitively binds to the NS3/4A protease complex, with K(i) values of 0.4 and 0.24 nM against recombinant enzymes representing genotypes 1a (H77) and 1b (J4L6S), respectively. Selectivity was demonstrated by the absence of any significant activity against the closely related GB virus-B NS3 protease and a panel of human serine or cysteine proteases. In cell culture, ASV inhibited replication of HCV replicons representing genotypes 1 and 4, with 50% effective concentrations (EC(50)s) ranging from 1 to 4 nM, and had weaker activity against genotypes 2 and 3 (EC(50), 67 to 1,162 nM). Selectivity was again demonstrated by the absence of activity (EC(50), >12 μM) against a panel of other RNA viruses. ASV exhibited additive or synergistic activity in combination studies with alfa interferon, ribavirin, and/or inhibitors specifically targeting NS5A or NS5B. Plasma and tissue exposures in vivo in several animal species indicated that ASV displayed a hepatotropic disposition (liver-to-plasma ratios ranging from 40- to 359-fold across species). Twenty-four hours postdose, liver exposures across all species tested were ≥110-fold above the inhibitor EC(50)s observed with HCV genotype-1 replicons. Based on these virologic and exposure properties, ASV holds promise for future utility in a combination with other anti-HCV agents in the treatment of HCV-infected patients.
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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.