| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Dasabuvir targets the HCV nonstructural protein 5B (NS5B) RNA-dependent RNA polymerase, an essential enzyme for viral RNA replication . It is a non-nucleoside inhibitor (NNI) that binds to the palm I site of the NS5B polymerase, an allosteric site distinct from the active site . In biochemical enzymatic assays, dasabuvir inhibits recombinant NS5B polymerases derived from HCV genotype 1a and 1b clinical isolates with IC50 values ranging from 2.2 to 10.7 nM . The compound demonstrates high selectivity for HCV genotype 1 polymerases, with selectivity ratios of at least 7,000-fold over human/mammalian polymerases (including DNA polymerases alpha, beta, gamma; RNA polymerases II and III; and polymerase gamma-RT function) . Additionally, preclinical studies have identified that dasabuvir can inhibit the hERG channel (IKr current) with a half-inhibitory concentration of 3.2 μM, which may contribute to cardiac action potential prolongation .
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|---|---|
| ln Vitro |
In biochemical enzymatic assays, dasabuvir inhibits HCV genotype 1a and 1b polymerases with IC50 values between 2.2 and 10.7 nM . The compound is at least 7,000-fold selective for HCV genotype 1 polymerases over human/mammalian polymerases . In HCV subgenomic replicon assays, dasabuvir inhibits genotype 1a (strain H77) and 1b (strain Con1) replication with EC50 values of 7.7 nM and 1.8 nM, respectively . In the presence of 40% human plasma, inhibitory potency decreases by approximately 12- to 13-fold, yielding EC50 values of 99 nM (genotype 1a) and 21 nM (genotype 1b) . Dasabuvir retains activity against a panel of chimeric subgenomic replicons containing NS5B genes from 22 genotype 1 clinical isolates from treatment-naive patients, with EC50 values ranging from 0.15 to 8.57 nM . Cytotoxicity testing reveals a CC50 of 10,360 nM, resulting in a therapeutic index exceeding 1,345 . Additionally, dasabuvir has been shown to inhibit replication of other flaviviruses, including Zika virus, West Nile virus, and tick-borne encephalitis virus, with EC50 values ranging from 9.09 to 10.85 μM . In canine left ventricular cardiomyocytes, dasabuvir inhibits hERG-channel-mediated ion current with an IC50 of 3.2 μM and prolongs action potential duration .
HCV genotype 1 polymerase is at least 7,000 times more specifically inhibited by dasabuvir (ABT-333) sodium than by human or animal polymerase [1]. With an IC50 ranging from 2.2 to 10.7 nM, dasabuvirodium reduces the polymerase activity of enzymes produced by the polymerase gene of HCV genotype 1 infected people as well as genotype 1 laboratory strain enzymes (H77, BK, N, and Con1 strains) [1]. In experiments conducted in cell culture, dasabuvirodium reduces HCV subgenomic replicon replication, with EC50 values for genotypes 1a (H77) and 1b (Con1), respectively, being 7.7 and 1.8 nM. The inhibitory activity of HCV genotype 1a (H77) and 1b (Con1) replicons fell 12- to 13-fold in the presence of 40% human plasma, with EC50s of 99 and 21 nM, respectively [1]. |
| ln Vivo |
In clinical studies, dasabuvir demonstrates potent antiviral activity in patients with chronic HCV genotype 1 infection. In a Phase 2a study, treatment-naive HCV-infected participants receiving dasabuvir (300 mg or 600 mg twice daily, or 1200 mg once daily) in combination with pegylated interferon and ribavirin achieved significant reductions in HCV RNA levels . Dasabuvir is highly effective when used as part of the “3D” regimen (dasabuvir, ombita svir, paritaprevir/ritonavir), achieving sustained virological response rates exceeding 95% in pooled analyses from six Phase 3 trials, including patients with compensated cirrhosis, HIV co-infection, and liver transplant recipients . In HCV genotype 1a patients, ribavirin is required as part of the regimen, while genotype 1b patients can be treated without ribavirin . The drug has been extensively evaluated in large clinical trials and demonstrates excellent efficacy in both treatment-naive and previously treated patients .
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| Enzyme Assay |
The inhibitory activity of dasabuvir against HCV NS5B polymerase was assessed using cell-free biochemical enzymatic assays with recombinant polymerases . Recombinant NS5B polymerases derived from HCV genotype 1a and 1b clinical isolates (including H77, BK, N, and Con1 strains) were expressed and purified. Polymerase enzymatic activity was measured by monitoring the incorporation of radiolabeled nucleotides into RNA templates. Dasabuvir was tested at various concentrations, and IC50 values (the concentration required to inhibit 50% of polymerase activity) were calculated from concentration-response curves using nonlinear regression analysis . Selectivity was assessed by testing dasabuvir against a panel of human and mammalian polymerases, including DNA-dependent DNA polymerases (alpha, beta, gamma), DNA-dependent RNA polymerases (II and III), and one RNA-dependent DNA polymerase (polymerase gamma-RT function), under similar assay conditions .
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| Cell Assay |
The antiviral activity of dasabuvir in cell culture was assessed using HCV subgenomic replicon systems . Huh7 cells (human hepatoma cells) harboring subgenomic HCV replicons expressing a luciferase reporter gene (genotype 1a strain H77 or genotype 1b strain Con1) were seeded in 96-well or 384-well assay plates. Cells were incubated with serially diluted dasabuvir (ranging from sub-nanomolar to micromolar concentrations) in DMEM containing 5% fetal bovine serum (FBS) with or without 40% human plasma for 3 days at 37°C in 5% CO₂ . After incubation, cells were lysed, and HCV replication was quantified by measuring firefly luciferase activity using a luminometer. EC50 values (the concentration required to reduce HCV RNA replication by 50%) were calculated by nonlinear regression curve fitting to a 4-parameter logistic equation using GraphPad Prism software . Cytotoxicity was assessed in parallel using MTT colorimetric assay or CellTiter-Glo to determine CC50 values .
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| Animal Protocol |
Specific detailed in vivo animal protocols for dasabuvir are not extensively described in the available literature; however, the compound has been characterized in human clinical trials . The clinical development of dasabuvir utilized standard pharmacokinetic and efficacy study designs in HCV-infected patients . In Phase 2a studies, HCV genotype 1-infected, treatment-naive participants received dasabuvir at doses of 300 mg or 600 mg twice daily or 1200 mg once daily for 2 days of monotherapy, followed by 26 days of combination therapy with pegylated interferon (180 μg subcutaneously once weekly) and ribavirin (1000 or 1200 mg daily divided twice daily) . Blood samples were collected at predefined time points (pre-dose; 2, 4, 8, 12, and 16 hours post-dose on Day 1; pre-dose on Day 2) for pharmacokinetic analysis, and HCV RNA levels were measured at serial time points to assess antiviral activity .
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| References | |
| Additional Infomation |
Drug Indications
Exviera is indicated for the treatment of chronic hepatitis C (CHC) in adults in combination with other drugs. It has specific activity against hepatitis C virus (HCV) genotypes. |
| Molecular Formula |
C26H28N3NAO5S
|
|---|---|
| Molecular Weight |
517.572396278381
|
| Exact Mass |
515.149
|
| CAS # |
1132940-11-4
|
| Related CAS # |
Dasabuvir;1132935-63-7; 1456607-55-8 (sodium monohydrate)
|
| PubChem CID |
56640145
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
5.697
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
36
|
| Complexity |
944
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O(C1C(=CC(N2C=CC(=O)NC2=O)=CC=1C1C=CC2C=C(NS(=O)(=O)C)C=CC=2C=1)C(C)(C)C)C.[NaH]
|
| InChi Key |
XHGMJAKIIJSQMF-UHFFFAOYSA-M
|
| InChi Code |
InChI=1S/C26H27N3O5S.Na/c1-26(2,3)22-15-20(29-11-10-23(30)27-25(29)31)14-21(24(22)34-4)18-7-6-17-13-19(28-35(5,32)33)9-8-16(17)12-18;/h6-15,28H,1-5H3,(H,27,30,31);/q;+1/p-1
|
| Chemical Name |
sodium;N-[6-[3-tert-butyl-5-(2,4-dioxopyrimidin-3-id-1-yl)-2-methoxyphenyl]naphthalen-2-yl]methanesulfonamide
|
| Synonyms |
Dasabuvir sodium; ABT-333 Sodium;ABT333 sodium; Dasabuvir sodium anhydrous; UNII-R2M8F5TK9T; R2M8F5TK9T; 1132940-11-4;
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9321 mL | 9.6605 mL | 19.3211 mL | |
| 5 mM | 0.3864 mL | 1.9321 mL | 3.8642 mL | |
| 10 mM | 0.1932 mL | 0.9661 mL | 1.9321 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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