HCV genotype 1b N(IC50=2.2 ± 0.3 nM);HCV genotype 1a H77(IC50=2.8 ± 0.2 nM);HCV genotype 1b BK(IC50=3.1 ± 0.21 nM);HCV genotype 1b Con1(IC50=0.7 ± 1.4 nM)
Dasabuvir (ABT-333): Hepatitis C virus (HCV) NS5B-encoded RNA-dependent RNA polymerase (IC50: 2.2–10.7 nM for recombinant NS5B polymerases from HCV genotype 1a and 1b clinical isolates; EC50: 7.7 nM for HCV genotype 1a (strain H77) replicon, 1.8 nM for HCV genotype 1b (strain Con1) replicon, 0.15–8.57 nM for chimeric subgenomic replicons with NS5B genes from 22 genotype 1 clinical isolates) [1]
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 .

Dasabuvir is at least 7,000-fold selective for the inhibition of HCV genotype 1 polymerases over human/mammalian polymerases. 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. Dasabuvir 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.

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1. Dasabuvir exhibited potent inhibitory activity against recombinant NS5B polymerases derived from HCV genotype 1a and 1b clinical isolates, with IC50 values ranging from 2.2 to 10.7 nM; the drug showed at least 7,000-fold selectivity for HCV genotype 1 polymerases over human and other mammalian polymerases, indicating minimal off-target effects on host enzymes [1]
2. In the HCV subgenomic replicon system, Dasabuvir inhibited viral replication in genotype 1a (H77 strain) and 1b (Con1 strain) replicons with EC50 values of 7.7 nM and 1.8 nM, respectively; the presence of 40% human plasma reduced its inhibitory potency by 13-fold, with the EC50 increasing to 100 nM for genotype 1a and 23 nM for genotype 1b replicons [1]
3. Against a panel of 22 chimeric subgenomic replicons carrying NS5B genes from treatment-naive HCV genotype 1 clinical isolates, Dasabuvir retained inhibitory activity with EC50 values spanning 0.15 to 8.57 nM, demonstrating efficacy against naturally occurring NS5B variants [1]
4. Long-term culture of replicon-containing cells in medium supplemented with Dasabuvir (at 10× or 100× the EC50) led to the emergence of resistant clones; sequencing of the NS5B coding region identified mutations including C316Y, M414T, Y448C/H, and S556G, all mapping to the palm I binding pocket of the NS5B polymerase [1]
5. Dasabuvir showed no cross-resistance with other HCV polymerase inhibitors: it retained full activity against replicons harboring the S282T mutation (a nucleoside inhibitor resistance variant) and thumb domain mutations (M423T, P495A/S, V499A) associated with resistance to other nonnucleoside inhibitors [1]

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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 .

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 .

the inhibition of human and mammalian DNA polymerases was evaluated by Replizyme Ltd. (Heslington, United Kingdom). The DNA-dependent RNA polymerase activity for human RNA polymerases II and III was measured using polymerases present in a HeLa cell extract and DNA templates containing promoters specific for either polymerase II or polymerase III. α-Amanitin, a potent inhibitor of human polymerase II and a modest inhibitor of polymerase III, was used as a control. The reaction mixtures contained 20 mM Tris-HCl (pH 8.0), 20% glycerol, 100 mM KCl, 1 mM dithiothreitol (DTT), 0.2 mM EDTA, 6 mM MgCl2, and either 1 μg/μl pAdVAntage plasmid (Promega, Madison, WI) (for the polymerase III assay) or 25 ng/μl cytomegalovirus (CMV) promoter DNA (Promega, Madison, WI) (for the polymerase II assay). The reaction mixtures also contained HeLa cell nuclear extract (ProteinOne, Rockville, MD), 400 μM ATP, CTP, and UTP, and 16 μM GTP and [α-33P]GTP. The reaction mixtures were incubated for 1 h at 30°C, quenched with the addition of proteinase K, SDS, and EDTA, incubated for 30 min at 56°C, and then analyzed on a Criterion Bio-Rad 5% acrylamide Tris-borate-EDTA (TBE)-urea gel. The gel was dried and placed on a PhosphorImager screen for overnight exposure. The volumes of the product bands were measured, and the percent inhibition was calculated; IC50 values were calculated using the following equation: % inhibition = 100[I]/([I] + IC50).

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1. To measure the inhibitory activity of Dasabuvir on HCV NS5B polymerase, recombinant NS5B proteins from HCV genotype 1a and 1b clinical isolates were purified and used in an in vitro polymerase activity assay; the assay utilized a radiolabeled RNA primer-template substrate, and the drug was incubated with the enzyme and substrate at 30°C for 1 hour. The incorporation of radioactive nucleotides into the RNA product was quantified by scintillation counting, and IC50 values were calculated from dose-response curves representing the percentage of enzyme activity relative to vehicle-treated controls [1]
2. For selectivity assessment, Dasabuvir was tested against a panel of human and mammalian polymerases (including DNA polymerases α, β, γ, and RNA polymerases I, II, III); the assay conditions were identical to the NS5B polymerase assay, and the concentration of Dasabuvir required to inhibit 50% of host polymerase activity was determined to calculate the selectivity ratio [1]

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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 .

Dasabuvir (ABT-333) is at least 7,000-fold selective for the inhibition of HCV genotype 1 polymerases over human/mammalian polymerases. Dasabuvir (ABT-333) 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. Dasabuvir (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.

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1. For the HCV replicon inhibition assay, Huh-7 cells stably expressing HCV genotype 1a (H77) or 1b (Con1) subgenomic replicons were seeded in 96-well plates and treated with serial dilutions of Dasabuvir for 72 hours. Viral RNA levels were quantified by real-time reverse transcription-PCR (RT-PCR), and cell viability was measured using a colorimetric assay to exclude cytotoxic effects. EC50 values for viral replication inhibition were calculated from the dose-response curves of viral RNA reduction [1]
2. To evaluate the impact of human plasma on Dasabuvir activity, replicon-containing cells were treated with the drug in medium supplemented with 0% or 40% human plasma; the assay was conducted as described above, and EC50 values were compared to assess plasma protein binding effects [1]
3. For resistance selection, replicon cells were cultured in 6-well plates with Dasabuvir at concentrations of 10× or 100× the EC50, with medium and drug refreshed every 3–4 days. Resistant colonies were picked after 2–4 weeks, expanded in culture, and the NS5B gene was amplified by RT-PCR and sequenced to identify mutations [1]
4. Cross-resistance studies were performed by treating replicon cells harboring known resistance mutations (S282T, M423T, P495A/S, V499A) with Dasabuvir; viral replication was quantified by RT-PCR, and EC50 values were compared to those of wild-type replicons to determine changes in susceptibility [1]

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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 .

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 .

Absorption, Distribution and Excretion
Dasabuvir reaches peak plasma concentration 4 hours after administration. The absolute bioavailability of dasabuvir is 70%. Dasabuvir is primarily excreted in feces (94.4%), with very little excretion in urine (2%). 26.2% and 0.03% of the drug are excreted unchanged in feces and urine, respectively, indicating that metabolism is the primary elimination pathway. The steady-state volume of distribution of dasabuvir is 149 liters. The clearance rate of dasabuvir has not been determined. Metabolism/Metabolites Dasabuvir is primarily metabolized via CYP2C8, with a small amount metabolized via CYP3A. Biological Half-Life The elimination half-life of dasabuvir is 5.5 to 6 hours.

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Dasabuvir is primarily eliminated via feces (94.4% of the administered radioactive dose) with minimal renal excretion (2.2%) . The biotransformation of dasabuvir primarily involves hydroxylation of the tert-butyl group to form the active metabolite M1 (N-(6-(5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3-(1-hydroxy-2-methylpropan-2-yl)-2-methoxyphenyl)naphthalen-2-yl)methanesulfonamide), followed by glucuronidation and sulfation of M1 . Dasabuvir is the major circulating component in plasma (58% of total radioactivity), followed by M1 (21%) . Dasabuvir is mainly metabolized by CYP2C8, followed by CYP3A4 . The absolute bioavailability of the dasabuvir 400 mg tablet is 46% . At therapeutic doses (250 mg twice daily recommended), peak plasma concentrations can reach the low micromolar range (approximately 1-4.2 μM depending on dose) . The elimination half-life is approximately 5-6 hours under normal conditions but can be significantly prolonged (up to 90 hours) when coadministered with strong CYP2C8 inhibitors such as gemfibrozil . No major accumulation is observed at doses up to 600 mg twice daily, but modest accumulation (65%) occurs at 1000 mg twice daily .

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Dasabuvir has not been studied in breastfeeding women receiving treatment for hepatitis C. Because it binds to maternal plasma proteins at a rate exceeding 99.5%, its concentration in breast milk may be very low. Breastfeeding does not need to be discontinued if the mother requires dasabuvir alone, or in combination with sofosbuvir or obitavir, paretamivir, and ritonavir (Vegirapak). Some sources suggest that breastfeeding should be avoided when dasabuvir is used in combination with ribavirin.
Ritonavir has been studied as a booster in several studies involving breastfeeding women. It is excreted into breast milk at measurable concentrations, and low concentrations of ritonavir have been detected in the blood of some breastfed infants. There have been no reports of adverse reactions in breastfed infants. For more information, please refer to the ritonavir record on the LactMed website. Hepatitis C is not transmitted through breast milk, and breast milk has been shown to inactivate the hepatitis C virus (HCV). However, the U.S. Centers for Disease Control and Prevention (CDC) recommends that mothers infected with HCV should consider discontinuing breastfeeding if they experience cracked or bleeding nipples. It is unclear whether this warning applies to mothers undergoing treatment for hepatitis C. Infants born to mothers infected with HCV should be tested for HCV; nucleic acid testing is recommended because maternal antibodies are present in the infant for the first 18 months after birth and until the infant develops an immune response. ◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on breastfeeding and breast milk
No published information found as of the revision date.

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Protein binding
Dasabuvir binds to human plasma proteins at a rate greater than 99.5%.

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Dasabuvir is generally well tolerated, with less than 1% of patients permanently discontinuing treatment due to adverse events and approximately 2% of patients experiencing a serious adverse reaction . Common adverse events are consistent with those expected from combination therapy. Dasabuvir is contraindicated in patients with known hypersensitivity to ritonavir (e.g., Stevens-Johnson syndrome) and strong inducers of CYP3A and CYP2C8 . Preclinical cardiac safety studies have identified that dasabuvir inhibits hERG channels (IKr current) with an IC50 of 3.2 μM and prolongs action potential duration in canine left ventricular cardiomyocytes, with early afterdepolarizations observed at concentrations of 3-30 μM . At therapeutic plasma concentrations (which can reach low μM levels, approximately 1-4.2 μM), dasabuvir may carry a risk of QT prolongation and cardiac arrhythmias, particularly in cases of overdose or coadministration with strong CYP2C8 inhibitors (e.g., gemfibrozil, clopidogrel) that can increase dasabuvir exposure more than 10-fold and prolong half-life from 5 to 90 hours . The FDA has issued warnings regarding the potential for QT prolongation with dasabuvir, especially when used with other drugs that affect CYP2C8 metabolism.

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

Dasabuvir belongs to the pyrimidinone class of drugs. Its sodium salt monohydrate form is used in combination with obitavir, paretavir, and ritonavir (trade name: Vickirapak) to treat chronic hepatitis C virus type 1 (HCV) infection and cirrhosis. It is an antiviral drug and a non-nucleoside hepatitis C virus polymerase inhibitor. It belongs to the naphthalene, sulfonamide, aromatic ether, and pyrimidinone class of compounds, and its structure is similar to uracil. Dasabuvir is a direct-acting antiviral drug used in combination therapy for chronic hepatitis C, an infectious liver disease caused by hepatitis C virus (HCV) infection. Hepatitis C virus (HCV) is a single-stranded RNA virus with nine different genotypes, of which genotype 1 is the most common in the United States, accounting for 72% of all chronic hepatitis C cases. Since 2011, significant progress has been made in the treatment of chronic hepatitis C with the development of direct-acting antiviral agents (DAAs) such as dasabuvir. Dasabuvir is a non-nucleoside NS5B inhibitor that binds to the palmar domain of NS5B, inducing a conformational change that prevents polymerase from elongating viral RNA. Because the binding sites of non-nucleoside NS5B inhibitors are poorly conserved across different HCV genotypes, dasabuvir is currently only applicable to genotype 1. In 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) jointly published guidelines recommending dasabuvir as a first-line treatment for hepatitis C virus genotype 1b, in combination with [DB09296], [DB09297], and [DB00503]; for genotype 1a hepatitis C virus, dasabuvir in combination with [DB00811] is recommended. Dasabuvir, [DB09296], [DB09297], [DB00503], and [DB00811] are used in combination to cure hepatitis C virus infection or achieve sustained virological response (SVR) after 12 weeks of treatment. SVR and eradication of hepatitis C virus infection are associated with significant long-term health benefits, including reduced liver-related damage, improved quality of life, reduced incidence of hepatocellular carcinoma, and reduced all-cause mortality. Dasabuvir is a fixed-dose combination product used in conjunction with [DB09296], [DB09297], and [DB00503] (brand name Viekira Pak) for the treatment of chronic hepatitis C. Viekira Pak was approved by the FDA in December 2014 for the treatment of HCV genotype 1a (including [DB00811]) or genotype 1b (excluding [DB00811]). Dasabuvir [DB09296], [DB09297], and [DB00503], when used in combination to form the combination formulation Viekira Pak, achieved a sustained virological response (SVR) of 100% in patients infected with genotype 1b hepatitis C virus (HCV) and an SVR of 89% or 95% in patients infected with genotype 1a HCV after 12 or 24 weeks of treatment, in a regimen containing [DB00811]. Dasabuvir is a non-nucleoside analogue hepatitis C virus (HCV) NS5B polymerase inhibitor. Its mechanism of action includes inhibition of RNA replicase, UGT1A1, and breast cancer resistance protein. Dasabuvir is a non-nucleoside analogue hepatitis C virus (HCV) nonstructural protein 5B (NS5B) inhibitor, an RNA-dependent RNA polymerase with potential anti-HCV activity. After administration, dasabuvir is absorbed intracellularly and binds to HCV NS5B polymerase, blocking viral RNA synthesis and replication. The HCV NS5B protein is essential for HCV RNA genome replication. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family. Hepatitis C virus (HCV) infection is closely associated with the development of hepatocellular carcinoma (HCC).

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Drug Indications
Dasabuvir, in combination with [DB09296], [DB09297], and [DB00503] (brand name Viekira Pak), is indicated for the treatment of patients with HCV genotype 1a carrying [DB00811] or HCV genotype 1b not carrying [DB00811], including patients with compensated cirrhosis.
FDA Label
Exviera, in combination with other drugs, is indicated for the treatment of chronic hepatitis C (CHC) in adults. It exhibits activity against specific hepatitis C virus (HCV) genotypes. Mechanism of Action Dasabuvir is a non-nucleoside HCV RNA-dependent RNA polymerase inhibitor. This enzyme, encoded by the NS5B gene, is crucial for viral genome replication. Based on resistance localization studies of HCV genotypes 1a and 1b, dasabuvir targets the palmar domain of the NS5B polymerase, hence its designation as a non-nucleoside NS5B palmar domain polymerase inhibitor. In HCV replicon cell culture assays, dasabuvir showed EC50 values of 7.7 nM and 1.8 nM against genotypes 1a-H77 and 1b-Con1, respectively. Dasabuvir induces conformational changes by binding to regions outside the NS5B enzyme active site, thereby preventing further elongation of the nascent viral genome. However, the binding sites outside the active site are poorly conserved across different viral genotypes, resulting in limited cross-genotype activity and an increased likelihood of resistance development. Therefore, dasabuvir is limited to the treatment of genotypes 1a and 1b and must be used in combination with other antiviral drugs.

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1. Dasabuvir (ABT-333) is a nonnucleoside inhibitor (NNI) that inhibits HCV NS5B RNA-dependent RNA polymerase by binding to the palmar I allosteric site of the enzyme, thereby blocking viral RNA synthesis[1]
2. Dasabuvir is part of a fixed-dose combination therapy with ABT-450 (an HCV NS3/4A protease inhibitor used in combination with ritonavir) and obitavir (an HCV NS5A inhibitor) for the treatment of chronic HCV genotype 1 infection[1]
3. The palmar I binding pocket of the NS5B polymerase targeted by dasabuvir is a conserved region, and resistance mutations in this region usually reduce the binding affinity of the drug but do not eliminate the function of the viral polymerase[1]

C26H27N3O5S

493.57

493.167

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

1132935-63-7

Dasabuvir sodium;1132940-11-4; 1456607-55-8 (sodium monohydrate)

56640146

White to off-white solid powder.

1.3±0.1 g/cm3

1.641

3.68

2

6

6

35

938

0

S(C([H])([H])[H])(N([H])C1C([H])=C([H])C2=C(C=1[H])C([H])=C([H])C(=C2[H])C1C([H])=C(C([H])=C(C=1OC([H])([H])[H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])N1C([H])=C([H])C(N([H])C1=O)=O)(=O)=O

NBRBXGKOEOGLOI-UHFFFAOYSA-N

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)

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

ABT333; ABT-333; ABT 333; Dasabuvir; 1132935-63-7; exviera; Trade names: Viekira Pak

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 46~98 mg/mL ( 93.20 ~198.55 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.07 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.07 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (5.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (5.07 mM)

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 (Please use freshly prepared in vivo formulations for optimal results.)