Dasabuvir | ABT-333 | CAS#1132935-63-7 (free base) | non-nucleoside polymerase inhibitor

MedKoo Cat#: 510275 | Name: Dasabuvir (ABT-333)

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

Dasabuvir (ABT-333)

CAS#1132935-63-7 (free base)

Theoretical Analysis

MedKoo Cat#: 510275

Name: Dasabuvir (ABT-333)

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

Chemical Formula: C26H27N3O5S

Exact Mass: 493.1671

Molecular Weight: 493.57

Elemental Analysis: C, 63.27; H, 5.51; N, 8.51; O, 16.21; S, 6.50

Price and Availability

Size	Price	Availability
25mg	USD 150.00	2 weeks
50mg	USD 250.00	2 weeks
100mg	USD 450.00	2 weeks
200mg	USD 750.00	2 weeks
500mg	USD 1,250.00	2 weeks
1g	USD 1,950.00	2 weeks
2g	USD 2,950.00	2 weeks
5g	USD 4,850.00	2 weeks
10g	USD 6,950.00	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

More Info

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/

	Solvent	mg/mL	mM
Solubility
	DMSO	55.0	111.43

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

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.

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:

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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Diagnosis and Management of Hepatitis C. Am Fam Physician. 2015 Jun 15;91(12):835-42. PMID: 26131943. 8: King JR, Zha J, Khatri A, Dutta S, Menon RM. Clinical Pharmacokinetics of Dasabuvir. Clin Pharmacokinet. 2017 Oct;56(10):1115-1124. doi: 10.1007/s40262-017-0519-3. PMID: 28258380. 9: Cada DJ, Baker DE, Bindler RJ. Ledipasvir/Sofosbuvir. Hosp Pharm. 2015 Mar;50(3):224-34. doi: 10.1310/hpj5003-224. PMID: 26405313; PMCID: PMC4567193. 10: Zeuzem S, Jacobson IM, Baykal T, Marinho RT, Poordad F, Bourlière M, Sulkowski MS, Wedemeyer H, Tam E, Desmond P, Jensen DM, Di Bisceglie AM, Varunok P, Hassanein T, Xiong J, Pilot-Matias T, DaSilva-Tillmann B, Larsen L, Podsadecki T, Bernstein B. Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014 Apr 24;370(17):1604-14. doi: 10.1056/NEJMoa1401561. Epub 2014 Apr 10. PMID: 24720679. 11: Poordad F, Hezode C, Trinh R, Kowdley KV, Zeuzem S, Agarwal K, Shiffman ML, Wedemeyer H, Berg T, Yoshida EM, Forns X, Lovell SS, Da Silva-Tillmann B, Collins CA, Campbell AL, Podsadecki T, Bernstein B. ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis. N Engl J Med. 2014 May 22;370(21):1973-82. doi: 10.1056/NEJMoa1402869. Epub 2014 Apr 11. PMID: 24725237. 12: Feld JJ, Kowdley KV, Coakley E, Sigal S, Nelson DR, Crawford D, Weiland O, Aguilar H, Xiong J, Pilot-Matias T, DaSilva-Tillmann B, Larsen L, Podsadecki T, Bernstein B. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014 Apr 24;370(17):1594-603. doi: 10.1056/NEJMoa1315722. Epub 2014 Apr 10. PMID: 24720703. 13: Hunyady B, Gerlei Z, Gervain J, Horváth G, Lengyel G, Pár A, Péter Z, Rókusz L, Schneider F, Szalay F, Tornai I, Werling K, Makara M. Hepatitis C-vírus- fertőzés: diagnosztika, antivirális terápia, kezelés utáni gondozás. 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