ABT-333

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.

Product information

CAS Number: 1132935-63-7

Molecular Weight: 493.57

Formula: C26H27N3O5S

Synonym:

Dasabuvir

ABT333

ABT 333

Chemical Name: N-{6-[3-tert-butyl-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-2-methoxyphenyl]naphthalen-2-yl}methanesulfonamide

Smiles: COC1C(=CC(=CC=1C(C)(C)C)N1C=CC(=O)NC1=O)C1=CC2=CC=C(C=C2C=C1)NS(C)(=O)=O

InChiKey: NBRBXGKOEOGLOI-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power

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

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

ABT-333 (Dasabuvir) is at least 7, 000-fold selective for the inhibition of HCV genotype 1 polymerases over human/mammalian polymerases. ABT-333 (Dasabuvir) inhibits the polymerase enzymatic activity of genotype 1 laboratory strain enzymes (H77, BK, N, and Con1 strains), as well as enzymes produced from polymerase genes from HCV genotype 1-infected subjects, with IC50s between 2.2 and 10.7 nM. ABT-333 inhibits 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. In the presence of 40% human plasma, there is a 12- to 13-fold decrease in inhibitory potency, yielding EC50s of 99 and 21 nM for HCV genotype 1a (H77) and 1b (Con1) replicons, respectively.

In Vivo:

The recombinant HCV polymerases used in this study contain the first 570 amino acids of the 591-amino acid native protein sequence, with a six-histidine tag at the N terminus to facilitate purification by affinity chromatography. Briefly, ABT-333 (Dasabuvir) is incubated with 5 to 50 nM polymerase for 15 min at room temperature, follow by the addition of nucleoside triphosphates (NTPs) and [3H]UTP for 3 h at 30°C. After termination of the reaction, the precipitated RNA is captured by filtration through a GF/B filter. The amount of incorporated [3H]UTP is measured by scintillation counting with a Wallac 1450 MicroBeta counter. The percent inhibition is calculated from the initial rates of inhibited reactions relative to that of the uninhibited control reaction. The mean 50% inhibitory concentration (IC50) and the standard error of the mean (SEM) are calculated via nonlinear regression.

References:

1. Kati W, et al. In vitro activity and resistance profile of dasabuvir, a nonnucleoside hepatitis C virus polymerase inhibitor. Antimicrob Agents Chemother. 2015 Mar;59(3):1505-11.

Products are for research use only. Not for human use.