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Dasabuvir (ABT-333)

Cat. No. M2333
Dasabuvir (ABT-333) Structure
Synonym:

Dasabuvir

Size Price Availability Quantity
Free Sample (0.5-1 mg)  USD 0 In stock
5mg USD 39.6  USD44 In stock
10mg USD 72  USD80 In stock
50mg USD 216  USD240 In stock
100mg USD 360  USD400 In stock
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Quality Control
Biological Activity

ABT-333 is a nonnucleoside NS5B polymerase inhibitor for the treatment of HCV infection. An interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the nonnucleoside polymerase inhibitor ABT-333, and ribavirin showed efficacy against the hepatitis C virus (HCV) in a pilot study involving patients with HCV genotype 1 infection. ABT-333 is currently under clinical trials for the treatment of Hepatitis C.

Protocol
Cell Experiment
Cell lines HCV replicon cells
Preparation method MTT analysis Both replicon-containing cell lines were maintained in Dulbecco’s modified Eagle’s medium (DMEM) containing 100 IU/ml penicillin, 100 g/ml streptomycin, and 200 g/ml G418 (all from Invitrogen, Carlsbad, CA) with 10% (vol/vol) fetal bovine serum (FBS).TheinhibitoryeffectsofdasabuvironHCVRNAreplication were determined in DMEM containing 5% FBS, with or without 40% human plasma (Bioreclamation, Westbury, NY), by measuring the activity of the luciferase reporter gene. The cells were incubated for 3 days in the presence of dasabuvir and subsequently were lysed and processed according to the manufacturer’s instructions (Promega, Madison, WI). The luciferase activity in the cells was measured using a Victor II luminometer (Perkin-Elmer, Waltham, MA); 50% effective concentration (EC50) values were calculated using nonlinear regression curve fitting to a 4-parameter logistic equation with GraphPad Prism 4 software. EC50s and standard deviations (SDs) were calculated from at least 3 experiments conducted in duplicate. The cytotoxicity of dasabuvir was determined with the colorimetric assay using MTT.
Concentrations Dasabuvir inhibited replication of HCV subgenomic replicons in cell culture assays, with EC50 values of 7.7 and 1.8 nM against genotype 1a (H77) and 1b (Con1), respectively.
Incubation time 3 days
Animal Experiment
Animal models none
Formulation
Dosages
Administration
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information
Molecular Weight 493.57
Formula C26H27N3O5S
CAS Number 1132935-63-7
Purity 100.00%
Solubility DMSO 26 mg/mL
Storage at -20°C
References

Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1.
Kowdley KV, et al. N Engl J Med. 2014 Jan 16;370(3):222-32. PMID: 24428468.

Exploratory study of oral combination antiviral therapy for hepatitis C.
Poordad F, et al. N Engl J Med. 2013 Jan 3;368(1):45-53. PMID: 23281975.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: Dasabuvir (ABT-333), Dasabuvir supplier, HCV Protease, inhibitors

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