Dasabuvir (ABT-333)
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MedKoo CAT#: 510275

CAS#: 1132935-63-7 (free base)

Description: Dasabuvir, also known as ABT-333, is a non-nucleoside polymerase inhibitor currently under clinical trials for the treatment of Hepatitis C. In the United States, it is approved by the Food and Drug Administration for use in combination with ombitasvir, paritaprevir, and ritonavir in the product Viekira Pak. Dasabuvir acts as a NS5B (an RNA-directed RNA polymerase) inhibitor.

Chemical Structure

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Dasabuvir (ABT-333)
CAS# 1132935-63-7 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 510275
Name: Dasabuvir (ABT-333)
CAS#: 1132935-63-7 (free base)
Chemical Formula: C26H27N3O5S
Exact Mass: 493.17
Molecular Weight: 493.575
Elemental Analysis: C, 63.27; H, 5.51; N, 8.51; O, 16.21; S, 6.50

Price and Availability

Size Price Availability Quantity
25mg USD 150 2 weeks
50mg USD 250 2 weeks
100mg USD 450 2 weeks
200mg USD 750 2 weeks
500mg USD 1250 2 weeks
1g USD 1950 2 weeks
2g USD 2950 2 weeks
5g USD 4850 2 weeks
10g USD 6950 2 weeks
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Related CAS #: 1456607-55-8 (sodium monohydrate)   1132935-63-7 (free base)  

Synonym: ABT333; ABT-333; ABT 333, Dasabuvir. Trade names: Viekira Pak (with ombitasvir/paritaprevir/ritonavir tablets), Exviera.

IUPAC/Chemical Name: N-(6-(3-(tert-butyl)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide

InChi Key: NBRBXGKOEOGLOI-UHFFFAOYSA-N

InChi Code: InChI=1S/C26H27N3O5S/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)

SMILES Code: CS(=O)(NC1=CC=C2C=C(C3=CC(N(C(N4)=O)C=CC4=O)=CC(C(C)(C)C)=C3OC)C=CC2=C1)=O

Appearance: white to off-white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO (40mg/mL)

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

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Product Data:
Product Data
Instruction:
View handling instruction
Biological target: Dasabuvir (ABT-333) is a nonnucleoside inhibitor of the RNA-dependent RNA polymerase encoded by the HCV NS5B gene that inhibits recombinant NS5B polymerases derived from HCV genotype 1a and 1b clinical isolates, with IC50 between 2.2 and 10.7 nM.
In vitro activity: Dasabuvir inhibited recombinant NS5B polymerases derived from HCV genotype 1a and 1b clinical isolates, with 50% inhibitory concentration (IC50) values between 2.2 and 10.7 nM, and was at least 7,000-fold selective for the inhibition of HCV genotype 1 polymerases over human/mammalian polymerases. In the HCV subgenomic replicon system, dasabuvir inhibited genotype 1a (strain H77) and 1b (strain Con1) replicons with 50% effective concentration (EC50) values of 7.7 and 1.8 nM, respectively, with a 13-fold decrease in inhibitory activity in the presence of 40% human plasma. This level of activity was retained against a panel of chimeric subgenomic replicons that contained HCV NS5B genes from 22 genotype 1 clinical isolates from treatment-naive patients, with EC50s ranging between 0.15 and 8.57 nM. Maintenance of replicon-containing cells in medium containing dasabuvir at concentrations 10-fold or 100-fold greater than the EC50 resulted in selection of resistant replicon clones. Consequently, dasabuvir retained full activity against replicons known to confer resistance to other polymerase inhibitors, including the S282T variant in the nucleoside binding site and the M423T, P495A, P495S, and V499A single variants in the thumb domain. Therefore, dasabuvir has the potential to play a key role in the treatment of HCV genotype 1 infections worldwide. Reference: Antimicrob Agents Chemother. 2015 Mar;59(3):1505-11. https://pubmed.ncbi.nlm.nih.gov/25534735/
In vivo activity: The method was applied to investigate the PK interaction between DSV and TAM/TOH following the co-administration of DSV and TAM to Wistar rats. Moreover, DSV had no significant effect on the degree of TAM metabolism since no significant change (p > 0.05) in metabolite/parent ratio (M.R. %) was observed. Similarly, TAM/TOH has an inhibitory effect on CYP3A4 enzymes and P-gp transporters. Giving that DSV is metabolized mainly by CYP2C8 and to a lesser extent by CYP3A4 and that it is transported mainly by P-gp transporters, TAM was expected to increase DSV exposure through P-gp inhibition and CYP3A4 inhibition. Yet, the animal experiments revealed the absence of any significant effect of TAM on any of the measured PK parameters of DSV. Reference: Sci Rep. 2020; 10: 3521. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044166/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 55.0 111.43

Preparing Stock Solutions

The following data is based on the product molecular weight 493.57 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Kati W, Koev G, Irvin M, Beyer J, Liu Y, Krishnan P, Reisch T, Mondal R, Wagner R, Molla A, Maring C, Collins C. In vitro activity and resistance profile of dasabuvir, a nonnucleoside hepatitis C virus polymerase inhibitor. Antimicrob Agents Chemother. 2015 Mar;59(3):1505-11. doi: 10.1128/AAC.04619-14. Epub 2014 Dec 22. PMID: 25534735; PMCID: PMC4325770. 2. Stefanik M, Valdes JJ, Ezebuo FC, Haviernik J, Uzochukwu IC, Fojtikova M, Salat J, Eyer L, Ruzek D. FDA-Approved Drugs Efavirenz, Tipranavir, and Dasabuvir Inhibit Replication of Multiple Flaviviruses in Vero Cells. Microorganisms. 2020 Apr 20;8(4):599. doi: 10.3390/microorganisms8040599. PMID: 32326119; PMCID: PMC7232190. 3. Almomen A, Maher HM, Alzoman NZ, Shehata SM, Al-Taweel SM, Alanazi AA. Development and validation of UPLC-MS/MS method for studying the pharmacokinetic interaction of dasabuvir and tamoxifen, 4-hydroxytamoxifen in Wistar rats. Sci Rep. 2020 Feb 26;10(1):3521. doi: 10.1038/s41598-020-60613-2. PMID: 32103133; PMCID: PMC7044166.
In vitro protocol: 1. Kati W, Koev G, Irvin M, Beyer J, Liu Y, Krishnan P, Reisch T, Mondal R, Wagner R, Molla A, Maring C, Collins C. In vitro activity and resistance profile of dasabuvir, a nonnucleoside hepatitis C virus polymerase inhibitor. Antimicrob Agents Chemother. 2015 Mar;59(3):1505-11. doi: 10.1128/AAC.04619-14. Epub 2014 Dec 22. PMID: 25534735; PMCID: PMC4325770. 2. Stefanik M, Valdes JJ, Ezebuo FC, Haviernik J, Uzochukwu IC, Fojtikova M, Salat J, Eyer L, Ruzek D. FDA-Approved Drugs Efavirenz, Tipranavir, and Dasabuvir Inhibit Replication of Multiple Flaviviruses in Vero Cells. Microorganisms. 2020 Apr 20;8(4):599. doi: 10.3390/microorganisms8040599. PMID: 32326119; PMCID: PMC7232190.
In vivo protocol: 1. Almomen A, Maher HM, Alzoman NZ, Shehata SM, Al-Taweel SM, Alanazi AA. Development and validation of UPLC-MS/MS method for studying the pharmacokinetic interaction of dasabuvir and tamoxifen, 4-hydroxytamoxifen in Wistar rats. Sci Rep. 2020 Feb 26;10(1):3521. doi: 10.1038/s41598-020-60613-2. PMID: 32103133; PMCID: PMC7044166.

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