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Synonyms | LY-570310, MP-424,VX-950 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C36H53N7O6 |
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分子量 | 679.85 | CAS No. | 402957-28-2 | |
Solubility (25°C)* | 体外 | DMSO | 136 mg/mL (200.04 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | Telaprevir is an HCV NS3-4A serine protease inhibitor with IC50 of 0.35 μM. |
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in vitro | Telaprevir inhibits the hepatitis C virus NS3-4A serine protease, leading to the block of viral polyprotein processing and subsequently decrease of viral RNA replication, total HCV RNA levels and protein levels in the Con1 (genotype 1b) subgenomic HCV replicon cells in a time- and dose-dependent manner. Telaprevir displays a significant time-dependent increase in inhibitory effect on the replication of HCV RNA with IC50 values of 0.574 μM, 0.488 μM, 0.210 μM and 0.139 μM for 24, 48, 72 and 120 hours incubation, respectively. Telaprevir displays an average IC50 of 0.354 μM and an average IC90 of 0.830 μM, respectively, from three independent experiments using the 48 hours incubation. Telaprevir has no significant cytotoxicity to HCV replicon cells, parental Huh-7 and HepG2 cells after 48 hours incubation. Telaprevir (17.5 μM) completely eradicates HCV RNA from replicon cells after 13 days incubation without rebound after Telaprevir is withdrawn. Telaprevir displays an additive to moderate synergistic effect on reduction of HCV RNA replication and suppression of resistance mutations without significant increase in cytotoxicity when in combination with IFN-α, compared to treatment with each agent alone. [1] |
in vivo | Oral administration of Telaprevir reduces HCV protease-dependent cleavage and subsequent secretion of SEAP from the liver into the blood in the mice model to 18.7% and 18.4% at dosage of 10 and 25 mg/kg, respectively. [2] Administration of Telaprevir at 200 mg/kg for 1 week results in a 1.9 log reduction of HCV RNA in genotype 1b HCV-infected human hepatocyte chimeric mice, and when treatment in combination with MK-0608 (50 mg/kg) for 4 weeks, viruses are eliminated from mice. [3] |
特徴 | Telaprevir is a covalent, reversible inhibitor of the NS3-4A protease (unlike BILN 2061which is a noncovalent inhibitor), with a slow-binding and slow-dissociation mechanism. |
キナーゼアッセイ | Determination of anti-HCV activity | |
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Stable Huh-7 cells containing the self-replicating, subgenomic HCV replicon, which is identical in sequence to the I377neo/NS3-3'/wt replicon are used for anti-HCV assays. Replicon cells are incubated at 37 °C for the indicated period of time with Telaprevir serially diluted in DMEM plus 2% FBS and 0.5% dimethyl sulfoxide (DMSO). Total cellular RNA is extracted using an RNeasy-96 kit, and the copy number of HCV RNA is determined using a quantitative RTPCR (QRT-PCR) assay for the assessment of 50% inhibitory concentration (IC50 | ||
細胞アッセイ | 細胞株 | Huh-7, HepG2, and peripheral blood mononuclear cells (PBMC) |
濃度 | Dissolved in DMSO, final concentration ~1 mM | |
反応時間 | 48 hours | |
実験の流れ | Cells are incubated with various concentrations of Telaprevir for 48 hours. Cell viability is determined by using a tetrazolium (MTS)-based cell viability assay. | |
動物実験 | 動物モデル | SCID mice injected with recombinant adenovirus (Ad-WT-HCVpro-SEAP or Ad-MT-HCVpro-SEAP) |
投薬量 | ~300 mg/kg | |
投与方法 | Oral gavage |
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Data from [Data independently produced by Antimicrob Agents Chemother, 2014, 10.1128/AAC.04220-14]
Data from [Data independently produced by Virology, 2013, 435(2), 385-94]
Data from [Data independently produced by PLoS One, 2013, 8(12), e82094]
Unraveling the dynamics of hepatitis C virus adaptive mutations and their impact on antiviral responses in primary human hepatocytes [ J Virol, 2024, e0192123.] | PubMed: 38319104 |
Hepatitis C virus cell culture adaptive mutations enhance cell culture propagation by multiple mechanisms but boost antiviral responses in primary human hepatocytes [ bioRxiv, 2023, 2023.11.22.568224] | PubMed: 38045248 |
The IDentif.AI-x pandemic readiness platform: Rapid prioritization of optimized COVID-19 combination therapy regimens [ NPJ Digit Med, 2022, 5(1):83] | PubMed: 35773329 |
The antiviral drug telaprevir induces cell death by reducing FOXA1 expression in estrogen receptor α (ERα)-positive breast cancer cells [ Mol Oncol, 2022, 16(19):3568-3584] | PubMed: 36056637 |
From Repurposing to Redesign: Optimization of Boceprevir to Highly Potent Inhibitors of the SARS-CoV-2 Main Protease [ Molecules, 2022, 27(13)4292] | PubMed: 35807537 |
Integrative multiomics and in silico analysis revealed the role of ARHGEF1 and its screened antagonist in mild and severe COVID-19 patients [ J Cell Biochem, 2022, 10.1002/jcb.30213] | PubMed: 35037717 |
Hepatitis C virus drugs that inhibit SARS-CoV-2 papain-like protease synergize with remdesivir to suppress viral replication in cell culture [ Cell Rep, 2021, 35(7):109133] | PubMed: 33984267 |
Pre-Senescence Induction in Hepatoma Cells Favors Hepatitis C Virus Replication and Can Be Used in Exploring Antiviral Potential of Histone Deacetylase Inhibitors [ Int J Mol Sci, 2021, 22(9)4559] | PubMed: 33925399 |
Pre-Steady-State Kinetics of the SARS-CoV-2 Main Protease as a Powerful Tool for Antiviral Drug Discovery [ Front Pharmacol, 2021, 12:773198] | PubMed: 34938188 |
Development of a Cell-Based Luciferase Complementation Assay for Identification of SARS-CoV-2 3CLpro Inhibitors [ Viruses, 2021, 13(2)173] | PubMed: 33498923 |
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人間や獣医の診断であるか治療的な使用のためにでない。
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