Telaprevir (VX-950)HCV NS3-4A protease inhibitor CAS# 402957-28-2 |
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Quality Control & MSDS
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| Cas No. | 402957-28-2 | SDF | Download SDF |
| PubChem ID | 3088969 | Appearance | Powder |
| Formula | C36H53N7O6 | M.Wt | 679.9 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Synonyms | VX-950 | ||
| Solubility | DMSO : ≥ 50 mg/mL (73.55 mM) H2O : < 0.1 mg/mL (insoluble) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | (3S,3aS,6aR)-2-[(2S)-2-[[(2S)-2-cyclohexyl-2-(pyrazine-2-carbonylamino)acetyl]amino]-3,3-dimethylbutanoyl]-N-[1-(cyclopropylamino)-1,2-dioxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-3-carboxamide | ||
| SMILES | CCCC(C(=O)C(=O)NC1CC1)NC(=O)C2C3CCCC3CN2C(=O)C(C(C)(C)C)NC(=O)C(C4CCCCC4)NC(=O)C5=NC=CN=C5 | ||
| Standard InChIKey | BBAWEDCPNXPBQM-IGSHNTALSA-N | ||
| Standard InChI | InChI=1S/C36H53N7O6/c1-5-10-25(29(44)34(48)39-23-15-16-23)40-33(47)28-24-14-9-13-22(24)20-43(28)35(49)30(36(2,3)4)42-32(46)27(21-11-7-6-8-12-21)41-31(45)26-19-37-17-18-38-26/h17-19,21-25,27-28,30H,5-16,20H2,1-4H3,(H,39,48)(H,40,47)(H,41,45)(H,42,46)/t22-,24-,25?,27-,28-,30+/m0/s1 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Telaprevir is a highly selective, reversible, and potent peptidomimetic inhibitor of the HCV NS3-4A protease, the steady-state inhibitory constant (Ki) of Telaprevir is 7 nM against a genotype 1 (H strain) NS3 protease domain plus a NS4A cofactor peptide.In Vitro:Telaprevir (VX-950) is a covalent, reversible inhibitor of the NS3-4A protease with a slow-binding and slow-dissociation mechanism. Telaprevir exhibits significantly different kinetics in enzyme inhibition, which is most clearly exemplified by a very long half-life (58 min) of the bound enzyme-inhibitor complex. Telaprevir is additive to moderately synergistic with IFN-α in inhibiting HCV replication and in suppressing the emergence of resistance in replicon cells. Telaprevir reduces HCV RNA levels in a time- and dose-dependent manner. The IC50s following a 24, 48, 72, and 120 h incubation with Telaprevir are determined to be 0.574, 0.488, 0.21, and 0.139 μM, respectively, indicating an increase in inhibitory effects with time. Following three independent experiments using the 48 h incubation in the presence of 2% FBS, the average IC50 of Telaprevir is determined to be 0.354 ± 0.035 μM, and the average IC90 is 0.830 ± 0.190 μM[1]. Telaprevir (VX-950) is a potent, selective, peptidomimetic inhibitor of the hepatitis C virus (HCV) NS3-4A serine protease, and Telaprevir demonstrates excellent antiviral activity both in genotype 1b HCV replicon cells (IC50=354 nM) and in human fetal hepatocytes infected with genotype 1a HCV-positive patient sera (IC50=280 nM)[2].In Vivo:There is an ~5-fold reduction of serum SEAP activity in mice dosed with Telaprevir (VX-950) at either 10 or 25 mg/kg, which has an average value (±SEM) of 18.7±8.3% or 18.4±5.4%, respectively, compare to those administered vehicle (100±28%). These data demonstrates that Telaprevir is able to inhibit the HCV NS3-4A serine protease activity in mouse liver and block cleavage and subsequent secretion of SEAP into blood circulation in these mice[2]. References: | |||||
Telaprevir (VX-950) Dilution Calculator
Telaprevir (VX-950) Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.4708 mL | 7.354 mL | 14.708 mL | 29.4161 mL | 36.7701 mL |
| 5 mM | 0.2942 mL | 1.4708 mL | 2.9416 mL | 5.8832 mL | 7.354 mL |
| 10 mM | 0.1471 mL | 0.7354 mL | 1.4708 mL | 2.9416 mL | 3.677 mL |
| 50 mM | 0.0294 mL | 0.1471 mL | 0.2942 mL | 0.5883 mL | 0.7354 mL |
| 100 mM | 0.0147 mL | 0.0735 mL | 0.1471 mL | 0.2942 mL | 0.3677 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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Telaprevir (also known as VX-950), derived from the viral NS5A/5B substrate of the protease through structure-based techniques, is a novel and potent inhibitor of hepatitis C virus (HCV) NS3-4A protease, which covalently and reversibly inhibit the NS3-4A protease via a slow-binding and slow-dissociation mechanism. Results of multiple studies show that telaprevir potently inhibits a genotype 1 (H strain) NS3 protease domain plus a NS4A cofactor peptide with the inhibitory constant (Ki) of 7 nM, exhibits strong anti-HCV in HCV replicon cells in vitro, and suppresses HCV replication as well as the emergence of resistance in HCV replicon cells with a synergistic effect with IFN-α.
Reference
Kai Lin, Robert B. Perni, Ann D. Kwong, and Chao Lin. VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCV replicon cells. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 2006; 50(5): 1813-1822
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Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C.[Pubmed:17879366]
Hepatology. 2007 Sep;46(3):640-8.
UNLABELLED: Telaprevir (VX-950), an inhibitor of the hepatitis C virus (HCV) NS3/4A protease, substantially decreased plasma HCV RNA levels in a prior clinical study. The present study evaluated viral kinetics and safety during dosing with telaprevir alone and in combination with peginterferon alfa-2a for 14 days. Previously untreated patients with genotype 1 hepatitis C were randomized to receive placebo and peginterferon alfa-2a (n = 4); telaprevir (n = 8); or telaprevir and peginterferon alfa-2a (n = 8). Telaprevir was given as 750 mg oral doses every 8 hours; peginterferon alfa-2a was given as weekly 180 mug subcutaneous injections. The median change in HCV RNA from baseline to day 15 was -1.09 log(10) (range, -2.08 to -0.46) in the placebo and peginterferon alfa-2a group; -3.99 log(10) (range, -5.28 to -1.26) in the telaprevir group, and -5.49 log(10) (range, -6.54 to -4.30) in the telaprevir and peginterferon alfa-2a group. Day 15 HCV RNA levels were undetectable in 4 patients who received telaprevir and peginterferon alfa-2a and in 1 patient who received telaprevir alone. No viral breakthrough occurred in patients who received telaprevir and peginterferon alfa-2a. The majority of adverse events were mild. There were no serious adverse events or premature discontinuations. Twelve weeks after starting off-study standard therapy, HCV RNA was undetectable in all 8 patients in the telaprevir and peginterferon alfa-2a group, 5 patients in the telaprevir group, and 1 patient in the placebo and peginterferon alfa-2a group. CONCLUSION: This study confirmed the substantial antiviral effects of telaprevir and showed an increased antiviral effect of telaprevir combined with peginterferon alfa-2a.
Highly sensitive determination of HCV protease inhibitors boceprevir (SCH 503034) and telaprevir (VX 950) in human plasma by LC-MS/MS.[Pubmed:19864192]
J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Dec 1;877(31):4001-6.
The purpose of this study was to develop a specific and highly sensitive method based on fast sample preparation and LC-MS/MS techniques for the determination of the HCV protease inhibitors boceprevir (SCH 503034) and telaprevir (VX 950) in human plasma. Boceprevir, telaprevir and the internal standard dimethylcelecoxib were separated on a Luna C18 column (150 mm x 2.0 mm I.D., 5 microm particle size) under gradient conditions with a mobile phase A consisting of water/ammonia solution (25%) (100:0.05, v/v) and mobile phase B consisting of methanol/ammonia solution (25%) (100:0.05, v/v) and a chromatographic run time of 11 min. The lower limit of quantification (LLOQ) of boceprevir and telaprevir is 0.25 pg on column (25 pg/mL at injection volume of 10 microL). The method possesses a reliable calibration range of 0.025-2.5 ng/mL. Due to the dilution of real life plasma samples by a factor of 10 during the precipitation process the method is suitable to quantify boceprevir and telaprevir at a concentration range of 0.25-25 ng/mL. Variations in accuracy and intraday and interday precision (n=6 for each concentration) were <15% over the whole range of calibration. For the first time, a rapid, specific, sensitive, accurate and reproducible LC-MS/MS method in human plasma has been developed and validated. It is suitable to quantify the concentrations of the hepatitis C virus protease inhibitors boceprevir and telaprevir in human plasma.
Genotype differences in susceptibility and resistance development of hepatitis C virus to protease inhibitors telaprevir (VX-950) and danoprevir (ITMN-191).[Pubmed:21480315]
Hepatology. 2011 Apr;53(4):1090-9.
UNLABELLED: Protease inhibitors (PIs) have proven to be effective adjuncts to interferon/ribavirin treatment of hepatitis C virus (HCV) infections. Little clinical or in vitro data exists, however, on their effectiveness for nontype 1 genotypes that predominate in Europe, the Middle East, Africa, and most of Asia. NS3 protease and NS4A genes from genotypes 1-6 were inserted into the JFH clone to generate replication-competent intergenotype chimeras. Susceptibility to PIs was determined by replication and infectivity assays. To study resistance development, chimeras were cultured in subinhibitory concentrations of PIs and mutations phenotypically characterized. Marked differences in susceptibility of different genotypes to danoprevir (ITMN-191) and Telaprevir (VX-950) were observed. Genotypes 1, 4, and 6 showed median inhibitory concentration (IC(50) ) values of 2-3 nM, >100-fold lower than genotypes 2/3/5 (250-750 nM). Telaprevir susceptibilities varied over a 4-fold range, with genotypes 1 and 2 being most susceptible and genotypes 4 and 5 most resistant. Culture of genotypes 1-6 in PIs induced numerous mutations in the NS3 protease domain, highly variable between genotypes. Introduction of danoprevir and BILN 2061-induced mutations into the original clones by site-directed mutagenesis (n = 29) all conferred resistant phenotypes, with particularly large increases (1-2 log greater IC(50) values) in the initially susceptible genotypes 1/4/6. Most introduced mutations and showed little or no effect on replicative fitness. CONCLUSION: Major differences were found between genotypes in their susceptibility and resistance development to PIs. However, equal sensitivities of genotypes 1, 4, and 6 to danoprevir and a broader efficacy range of telaprevir between genotypes than initially conceptualized provide strong evidence that PIs might be effectively used beyond their genotype 1 target group.
Inflammatory markers neopterin and alanine aminotransferase in HCV patients treated with HCV NS3.4A protease inhibitor telaprevir (VX-950) and/or peginterferon alfa-2a.[Pubmed:18609142]
Scand J Gastroenterol. 2008;43(9):1122-7.
OBJECTIVE: Neopterin is a marker of monocyte/macrophage activity. Alanine aminotransferase (ALAT) is a marker of hepatocyte injury. The aim of this study was to determine changes in neopterin and ALAT levels, as markers of inflammation, in two ancillary studies during two-phase 1b trials of hepatitis C virus (HCV) NS3.4A protease inhibitor Telaprevir (VX-950), with or without peginterferon alfa-2a (Peg-IFN). MATERIAL AND METHODS: Fifty-four chronic hepatitis C patients (genotype 1) received placebo or telaprevir, with or without Peg-IFN, for 14 days in two multiple-dose studies. RESULTS: During administration of telaprevir, every patient demonstrated a >2-log decrease in HCV RNA. Mean neopterin and ALAT levels decreased in all four groups receiving telaprevir alone. In contrast, mean neopterin levels increased and ALAT levels decreased in the Peg-IFN plus telaprevir and Peg-IFN plus placebo groups. CONCLUSIONS: These data suggest that treatment of chronic hepatitis C patients with an HCV NS3.4A protease inhibitor ameliorates inflammation. The increase in neopterin levels and the decrease in ALAT levels during administration of Peg-IFN with or without telaprevir are in accordance with earlier observations showing that IFN reduces hepatocyte injury but increases monocyte/macrophage activity. The IFN-mediated immunomodulatory effects appear to remain intact when IFN is combined with telaprevir.
