- |||||||||| Olysio (simeprevir) / J&J, Medivir
Journal: PREINCUBATION-DEPENDENT INHIBITION OF ORGANIC ANION TRANSPORTING POLYPEPTIDE 2B1. (Pubmed Central) - Jul 28, 2024 In conclusion, preincubation resulted in inhibitor- and substrate-dependent inhibition of OATP2B1. These results support the conclusion that to reduce the risk of false negative DDI prediction, preincubation should be considered also in OATP2B1 inhibition assays.
- |||||||||| Olysio (simeprevir) / J&J, Medivir, Daklinza (daclatasvir) / BMS
PK/PD data, Journal: Synchronous spectrofluorimetry and chemometric modeling: A synergistic approach for analyzing simeprevir and daclatasvir, with application to pharmacokinetics evaluation. (Pubmed Central) - Apr 6, 2024 Moreover, the proposed models have been applied to determine the pharmacokinetics of simeprevir and daclatasvir, providing valuable insights into their distribution and elimination patterns. Overall, the study demonstrates the effectiveness of synchronous spectrofluorimetry coupled with multivariate calibration optimized by firefly algorithms in accurately determining and quantifying simeprevir and daclatasvir in HCV antiviral treatment, offering potential applications in pharmaceutical formulation analysis and pharmacokinetic studies for these drugs.
- |||||||||| Review, Journal: Update on monkeypox virus infection: Focusing current treatment and prevention approaches. (Pubmed Central) - Jan 16, 2024
Overall, the study demonstrates the effectiveness of synchronous spectrofluorimetry coupled with multivariate calibration optimized by firefly algorithms in accurately determining and quantifying simeprevir and daclatasvir in HCV antiviral treatment, offering potential applications in pharmaceutical formulation analysis and pharmacokinetic studies for these drugs. This review highlights the pathogenesis of the virus, disease manifestations, drugs, and vaccines that are being used and those under pipeline for the treatment and prevention of Mpox.
- |||||||||| Olysio (simeprevir) / J&J, Medivir
Journal: Cryo-EM structures of human organic anion transporting polypeptide OATP1B1. (Pubmed Central) - Dec 17, 2023 These structures reveal major and minor substrate binding pockets and conformational changes during transport. In combination with mutagenesis studies and molecular dynamics simulations, our work comprehensively elucidates the transport mechanism of OATP1B1 and provides the structural basis for DDI predictions involving OATP1B1, which will greatly promote our understanding of OATPs.
- |||||||||| Olysio (simeprevir) / J&J, Medivir
Journal, Gene therapy: A simeprevir-inducible molecular switch for the control of cell and gene therapies. (Pubmed Central) - Nov 28, 2023 Here we describe a CID module based on the orally available, approved, small molecule simeprevir and its target, the NS3/4A protease from hepatitis C virus. We demonstrate the utility of this CID module as a molecular switch to control biological processes such as gene expression and apoptosis in vitro, and show that the CID system can be used to rapidly induce apoptosis in tumor cells in a xenograft mouse model, leading to complete tumor regression.
- |||||||||| HTMC0435 / Shanghai Huilun
Enrollment open: HTMC0435 and Temozolomide in Treating Patients With Small Cell Lung Cancer (clinicaltrials.gov) - Sep 28, 2023 P1b/2, N=64, Recruiting, RAASs in NS3, NS5A, and NS5B reduce the susceptibility to DAAs; therefore, continuous RAAS-dependent resistance profiling in HCV is recommended to minimize the probability of DAA therapeutic failure. Not yet recruiting --> Recruiting
- |||||||||| Olysio (simeprevir) / J&J, Medivir
Preclinical, Journal: Inhibitory effects of simeprevir on Staphylococcusepidermidis and itsbiofilm in vitro. (Pubmed Central) - Aug 16, 2023 In conclusion, the simeprevir PBPK model developed in this study can quantitatively describe the increase in exposures of concomitant drugs and an endogenous biomarker via inhibition of CYP3A4 and OATP1B. Simeprevir shows antimicrobial effect and anti-biofilm activities against S. epidermidis.
- |||||||||| Journal: Development of an assay pipeline for the discovery of novel small molecule inhibitors of human glutathione peroxidases GPX1 and GPX4. (Pubmed Central) - Jun 7, 2023
Two compounds (metamizole sodium and isoniazid sodium methanesulfate) inhibited all three GPXs but not TXNRD1, while 2,3-dimercaptopropanesulfonate, PI4KIII beta inhibitor 3, SCE-2174 and cefotetan sodium inhibited all tested selenoproteins (but not GR)...With this approach, we could indeed identify novel GPX1/GPX2- or GPX4-specific inhibitors, thus presenting a validated pipeline for future identification of specific selenoprotein-targeting agents. Our study also identified GPX1/GPX2, GPX4 and/or TXNRD1 as targets for several previously developed pharmacologically active compounds.
- |||||||||| Olysio (simeprevir) / J&J, Medivir
Journal: Simultaneous spectrofluorimetic determination of remdesivir and simeprevir in human plasma. (Pubmed Central) - Dec 21, 2022 The high sensitivity of the developed method permitted the simultaneous determination of both drugs in spiked plasma samples with % recoveries ranging from 95.0 to 103.25 with acceptable standard deviation values of 1.92 and 3.04 for remdesivir and simeprevir, respectively. The validation of the approach was approved by the International Council of Harmonization (ICH) guidelines.
- |||||||||| Sunvepra (asunaprevir) / BMS, Olysio (simeprevir) / J&J, Medivir, Daklinza (daclatasvir) / BMS
Journal: Going Viral: An Investigation into the Chameleonic Behavior or Antiviral Compounds. (Pubmed Central) - Oct 27, 2022 No significant differences in size and polar surface area were observed between the DMSO- d 6 and chloroform ensembles of these three drugs. We propose that such flexible compounds are characterized as "partial molecular chameleons" and hypothesize that their ability to adopt conformations with low polar surface area contributes to their membrane permeability and oral absorption.
- |||||||||| Olysio (simeprevir) / J&J, Medivir
Journal: Repurposing of HIV/HCV protease inhibitors against SARS-CoV-2 3CL. (Pubmed Central) - Oct 18, 2022 HCV protease inhibitor simeprevir showed the most potency against 3CL with an EC vale of 2.6 μM, bound to the active site pocket of 3CL in a predicted model, and importantly, exhibited a similar activity against the protease containing the mutations P132H in Omicron variants. Taken together, this work demonstrates the feasibility of using the cell-based BRET assay for screening 3CL inhibitors and supports the potential of simeprevir for the development of 3CL inhibitors.
- |||||||||| remdesivir / Generic mfg.
Journal: Effectiveness of Remdesivir in Comparison with Five Approved Antiviral Drugs for Inhibition of RdRp in Combat with SARS-CoV-2. (Pubmed Central) - Oct 4, 2022 Also, the results show that the number of H-bonds and contacts and ∆G interactions between the protein and ligand in the Remdesivir complex is less than those of other complexes. According to the given data which shows the tendency of binding with RdRp for Paritaprevir, Simeprevir, Glecaprevir, and Ledipasvir and Elbasvir is more than Remdesivir and due to the fact that these five drugs have a high tendency to bind to other targets in the SARS-CoV-2, the use of Remdesivir as an antiviral drug in the treatment of COVID-19 should be considered more sensitively.
- |||||||||| Journal: Meta-Data Analysis to Explore the Hub of the Hub-Genes That Influence SARS-CoV-2 Infections Highlighting Their Pathogenetic Processes and Drugs Repurposing. (Pubmed Central) - Aug 27, 2022
Then we detected hHub-DEGs guided top-ranked nine candidate drug agents (Digoxin, Avermectin, Simeprevir, Nelfinavir Mesylate, Proscillaridin, Linifanib, Withaferin, Amuvatinib, Atazanavir) by molecular docking and cross-validation for treatment of SARS-CoV-2 infections. Therefore, the findings of this study could be useful in formulating a common treatment plan against SARS-CoV-2 infections globally.
- |||||||||| Ganovo (danoprevir) / Roche, Ascletis, Pfizer, Olysio (simeprevir) / J&J, Medivir
Journal: A fuzzy logic-based computational method for the repurposing of drugs against COVID-19. (Pubmed Central) - Aug 22, 2022 It can be concluded that the similarity-based drug repurposing techniques may be the most suitable option for managing emerging diseases such as COVID-19 and can be applied to a wide range of data. Also, fuzzy logic-based scoring methods can produce outcomes which are more consistent with the real-world biological applications than others.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte, Olysio (simeprevir) / J&J, Medivir, Tasigna (nilotinib) / Novartis, Inhibikase
FDA event, Journal: Repurposing of FDA-approved drugs as autophagy inhibitors in tumor cells. (Pubmed Central) - Jul 23, 2022 We anticipate from our computational results that these drugs may become potent candidates to inhibit autophagy and exhibit the apoptosis in the tumor microenvironment and combat the current limitation of potent autophagy inhibitors; however, to substantiate our in-silico results, further experimental validations of these drug molecules are currently in progress. Communicated by Ramaswamy H. Sarma.
- |||||||||| Invirase (saquinavir) / Roche, Olysio (simeprevir) / J&J, Medivir
Journal: Repurposing antiviral drugs against HTLV-1 protease by molecular docking and molecular dynamics simulation. (Pubmed Central) - May 26, 2022 The MD simulation confirmed the stability of Simeprevir-protease, Atazanavir-Protease, and Saquinavir-Protease interactions. Clearly, these compounds should be further evaluated in experimental assays and clinical trials to confirm their actual activity against HTLV-1 infection.Communicated by Ramaswamy H. Sarma.
- |||||||||| Preclinical, Journal: In Vitro Assessment of Transporter Mediated Perpetrator DDIs for Several Hepatitis C Virus Direct-Acting Antiviral Drugs and Prediction of DDIs with Statins Using Static Models. (Pubmed Central) - May 6, 2022
Inhibitory effects of asunaprevir, daclatasvir, grazoprevir, paritaprevir, simeprevir, and voxilaprevir, direct-acting antiviral (DAA) drugs for the treatment of chronic hepatitis C virus (HCV) infection, were evaluated in vitro against a range of clinically important drug transporters...Furthermore, we refined and developed static models to predict complex DDIs with several statins (pitavastatin, rosuvastatin, atorvastatin, and pravastatin) by mechanistically assessing differential inhibitory effects of perpetrator drugs on multiple transporters, such as organic anion transporting polypeptides (OATP1B), breast cancer resistance protein (BCRP), multidrug resistance protein 2 (MRP2), organic anion transporter 3 (OAT3), and cytochrome P450 CYP3A enzyme, as they are known to contribute to absorption, distribution, metabolism and excretion (ADME) of above statins...Our studies suggest that mechanistic static model is a promising and useful tool to provide more accurate prediction of the risk and magnitude of DDIs with statins in early drug development and may help to improve the management of clinical DDIs for HCV drugs to ensure effective and safe HCV therapy. GRAPHICAL ABSTRACT.
- |||||||||| Olysio (simeprevir) / J&J, Medivir
Journal: Enhanced fitness of hepatitis C virus increases resistance to direct-acting antivirals. (Pubmed Central) - Mar 8, 2022 Beneficial substitutions hyperstimulated phosphatidylinositol 4-phosphate during DAA treatment, and showed decreased dependence on cyclophilins during cyclosporine A treatment, indicating an interplay of virus-host molecular mechanisms in beneficial substitution selection that may necessitate infectious virus production. This comprehensive study demonstrates a possible role for HCV fitness of overcoming drug-mediated selection pressure.
- |||||||||| Olysio (simeprevir) / J&J, Medivir
Preclinical, Journal: Effects of simeprevir on the replication of SARS-CoV-2 in vitro and in transgenic hACE2 mice. (Pubmed Central) - Jan 21, 2022 In a transgenic hACE2 mouse model of SARS-CoV-2 infection, intraperitoneal administration of simeprevir at 10 mg/kg/day for 3 consecutive days failed to suppress viral replication. These findings collectively imply that simeprevir does not inhibit SARS-CoV-2 in vivo and therefore do not support its application as a treatment against COVID-19 at a dosage of 10 mg/kg/day.
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