HCV 1a (EC50 = 4 nM); HCV 1b (EC50 = 3 nM); HCV 2a (EC50 = 3 nM)

Elbasvir exhibits strong activity against the 1a and 1b genotype replicons, as evidenced by its EC90 of 0.006 nM for the 1a_H77 wild-type and 1b_con1 replicons. With an EC90 of 0.12 nM, elasvir inhibits genotype 3 replicons. The decreases in colony counts at higher doses of elbasvir (0.06 nM, 0.6 nM, and 6 nM) show dose-dependent suppression of resistant genotype 1a replicons. With EC50s in the low-picomolar range, elbasvir exhibits high potency against HCV replicons carrying NS5A sequences from GT1a, -1b, -2a(31L), -3a, -4a, -5a, and -6.

Phase 1b clinical trial results. (i) Subject accounting.[1]
A total of 48 patients received Elbasvir or placebo in an elbasvir dose-ranging study, including 17 patients with genotype 1a, 13 patients with genotype 1b, and 18 with genotype 3. All patients completed the 5-day course of therapy. Mislabeling of 7 samples from 3 patients (1 each infected with genotype 1a, 1b, or 3) occurred at the sequencing facility; these samples were therefore excluded from the analysis. Baseline virus from 1 additional genotype 3 patient could not be amplified. Consequently, only sequence data from the other 44 patients (including 16 with genotype 1a, 12 with genotype 1b, and 16 with genotype 3) were used for the resistance analyses.

Variants with NS5A substitutions at positions 28, 30, 58, and 93 (which had been previously identified as potential RAVs for NS5A inhibitors) were detected at baseline in 7 of 44 patients (15.9%) (Table 6). Except for possibly 1 patient infected with genotype 3 in the 10-mg Elbasvir dose group, baseline NS5A variants did not appear to impact the magnitude of viral load reduction during treatment. In particular, M28V or Q30R in genotype 1a and Y93H in genotype 1b at baseline had little impact on the magnitude of viral load reduction during treatment.

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(ii) Genotype 1 infections.[1]
All doses of Elbasvir led to rapid HCV RNA reductions of 3.7 to 5.1 log10 IU/ml in genotype 1 infections. At the same dose, larger viral load reductions were achieved in genotype 1b infections than in infections with genotype 1a. The viral load decline after discontinuation of 5-day elbasvir monotherapy was more sustained in genotype 1b patients than in genotype 1a patients at the same elbasvir dose. In general, the types and prevalence of postbaseline RAVs selected within each subgenotype were similar across dosing levels.

In the 2 genotype 1a patients with pretreatment M28V or Q30R polymorphisms, >3-log viral load reductions were achieved with 5 mg and 50 mg dosing of Elbasvir, respectively. In the patient with baseline M28V (which did not confer elbasvir resistance in vitro) treated with the 5-mg dose of elbasvir, Q30H/Q and L31L/V were additionally detected during the posttreatment follow-up period along with M128V/A. Clonal analysis identified linkages between M28Vand L31V as well as between M28A and Q30H, but no linkage was found between L31V and Q30H. Only M28V was detectable at the last follow-up on day 61 by population sequencing. In the genotype 1a patient with baseline Q30R (associated with a 24-fold increase in elbasvir EC90 in vitro) treated with the 50-mg dose of elbasvir, Q30R was detected with L31V from the end of treatment until the last follow-up on day 56. Clonal sequencing was not performed for this patient. One genotype 1b patient with Y93H/Y and A92T/A mixtures at baseline treated with the 50-mg dose of elbasvir achieved a >4-log viral load reduction (even though Y93H was associated with a 67-fold increase in elbasvir EC90 in vitro). After treatment cessation, clonal sequencing identified L28M linked to Y93H and L31V linked to A92K, without linkage between Y93H and either L31V or A92K. At the last visit on day 59, only the Y93H/Y and L31V/L mixtures were detected by population sequencing.

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(iii) Genotype 3 infections.[1]
Antiviral responses were less robust for genotype 3 than for genotype 1 infections in the 10-mg Elbasvir dosing group, but mean HCV RNA reductions of ∼3 log were achieved at the 50- and 100-mg doses (3). Posttreatment Y93H was found in all 10 patients in the 50- and 100-mg elbasvir dose groups and persisted through the last follow-up in each case. L31F was also detected in 2 of these patients.

One of the 3 evaluated patients with genotype 3 infection in the 10-mg dose group harbored a baseline A30A/E/K/T mixture and had a <1-log10 IU/ml reduction in the level of HCV RNA at nadir compared to a mean 1.43-log10 drop in viremia in the other 2 patients in the 10-mg dosing group without detectable RAVs at baseline. Population sequencing showed that A30A/E/K/T converted to A30K (which conferred a 41-fold increase in Elbasvir EC90 in vitro) from treatment discontinuation through the last follow-up on day 61.

Elbasvir is an HCV NS5A inhibitor that, depending on genotype, has a median EC50 value ranging from 0.2 to 3600 pmol/L. It inhibits the replication of the hepatitis C virus and the assembly of virion.

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HCV replicons were used to determine the effective concentrations (EC) of Elbasvir necessary to inhibit HCV RNA levels by a specified percentage (50% or 90%) for genotypes 1a, 1b, and 3 variants compared to no treatment. Replicons maintained in 0.5 mg/ml of G418 to select replicating cells were seeded on 384-well plates in Dulbecco's modified Eagle medium (DMEM) containing 5% fetal calf serum. Twofold dilutions of elbasvir concentrations from 1 μM down to 0.002 μM were added to the medium the next day in the presence of 0.5% dimethyl sulfoxide (DMSO). After 72 h of incubation, cells were harvested and subjected to real-time reverse transcriptase PCR (RT-PCR). For each variant, threshold cycle numbers were plotted against the log of elbasvir concentrations and fitted to a sigmoid dose-response curve using Prism to obtain the EC50 and EC90 (the drug concentrations needed to achieve 50% and 90% inhibition, respectively, relative to a DMSO control without drug). For reference, the steady-state minimum concentration (Cmin) for once-daily 50 mg elbasvir dosing is about 22 nM [1].

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Kinetic analysis of the combination of grazoprevir and Elbasvir in GT1a. [2]
The “independent-effects” definition of additive response was used to assess the nature of inhibitor interactions (synergistic, additive, or antagonistic). Inhibitor interactions were analyzed with the aid of MacSynergy software, which requires input data in linear scale. To fulfill that requirement the log-scale measurements of threshold cycle number (CT) were converted into relative amounts of RNA using the standard curves from the same assay plate. The standard curves were constructed with total RNA isolated from replicon cells and then serially diluted. The relative amount of replicon RNA from each sample (treated cells in each well) was calculated based on the CT of the sample and the standard curve from the same plate. MacSynergy calculates an additive response at each combination and defines synergy as a response that exceeds additivity and antagonism as a response that is less than additivity. The application then calculates synergy/antagonism volumes at a ≥95% confidence interval and categorizes the results as synergy, additivity, or antagonism.

To select cell lines with decreased Elbasvir susceptibility, subconfluent monolayers of replicon cells were cultured in the presence of various drug concentrations at multiples of EC90. Plates were prepared at 2 × 105 cells per 60-mm plate and passaged only once at a 1:10 ratio when the cells reached 95% confluence. Colonies surviving selection were first counted and then pooled and expanded for analysis. The colony count in the presence of elbasvir was divided by the number of cells seeded to calculate resistance frequency. Total cellular RNA was isolated from pooled colonies and amplified by RT-PCR. The RT-PCR products were purified with a QIAquick PCR purification kit, and the full-length NS5A gene was sequenced. Additionally, the RT-PCR products were cloned into the TOPO TA vector, and the plasmid DNA from bacterial colonies was sequenced to look for linked variations. The replicative capacity (“fitness”) of RAVs was evaluated in a replicon colony formation assay [1].

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Stable-replicon assay. [2]
Stable-replicon cell lines were tested for compound sensitivity. Briefly, replicon cells were seeded in 384-well plates in Dulbecco modified Eagle medium (DMEM) containing 0.5 mg/ml G-418. Concentrations spanning the 50% effective concentration (EC50) for each compound were used independently or in the combination studies for grazoprevir and Elbasvir. The compounds were serially diluted individually in 100% dimethyl sulfoxide (DMSO) and then were added to the medium in the presence of 5% fetal calf serum (FCS) with cells in 1:200 dilutions on the day after cells were seeded. The final DMSO concentration was 0.5% (vol/vol). After 72 h of incubation, cells were harvested and subjected to real-time PCR analysis as reported previously. The primer/probe sets used for the PCR analysis on an ABI Prism 7900HTS sequence detection system are listed in Table S2 in the supplemental material. The independent and combination studies were tested 3 times with triplicate plates in each experiment (or run).

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Long-term viral kinetic studies. [2]
Stable-replicon cells were seeded in 6-well plates at various cell concentrations for confluence at harvest and then dosed 6 h later at 1× EC90 with grazoprevir and Elbasvir independently for a final DMSO concentration of 0.5% (vol/vol) in DMEM containing 10% fetal bovine serum (FBS) without G418. Treated cells were harvested with trypsin-EDTA (0.25%) at 0, 24, 48, 72, 96, 168, 240, and 336 h (with cell passing at 72, 168, and 240 h), and RNA was isolated utilizing the RNeasy purification kit via the manufacturers protocol. RNA was then subjected to real-time PCR analysis as reported previously using the above-mentioned primers and probes. The threshold cycle numbers (CT) were normalized to the GAPDH (glyceraldehyde-3-phosphate dehydrogenase) housekeeping gene to yield ΔCT, and the log(1/power) (2,ΔCT − average ΔCT of DMSO at day zero) was plotted over time using Prism.

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Compound treatment to select for emergence of resistance. [2]
GT1a subgenomic replicon cells were seeded onto multiple 6-cm tissue culture dishes at a density of 2 × 105 cells/dish. Four dishes were prepared for each treatment condition. Twenty-four hours after plating, cells were dosed with various combinations and multiples of the EC90 values of grazoprevir and Elbasvir (as indicated in appropriate tables and figures). Media and compounds were refreshed twice a week. In the event that the monolayer reached confluence (e.g., with the DMSO treatment control), those cells were passaged at a 1:10 ratio. At about 3 to 4 weeks postinitiation, when resistant replicon cells formed defined colonies, 3 of the 4 dishes were fixed and stained with a crystal violet solution for colony counting. Cells on the remaining dish were expanded for further analysis (i.e., sequencing of reverse transcription-PCR [RT-PCR] products and phenotypic sensitivity to compounds).

Phase 1b randomized clinical trial design. [1]
MK-8742 P002 was a randomized, double-blind, placebo-controlled, sequential dose-escalating phase 1b study of Elbasvir monotherapy to assess safety, pharmacokinetics, and viral responses in adult men with chronic HCV-1 or HCV-3 infection. Patients between 18 and 60 years of age (up to 65 years old at the discretion of the investigator) with HCV RNA levels of >100,000 IU/ml were eligible. Elbasvir doses were 5, 10, and 50 mg once daily for patients infected with genotype 1a or 1b, and 10, 50, and 100 mg once daily for patients infected with genotype 3. A total of 6 patients were to be enrolled at each dosing level, including 5 patients to receive elbasvir and 1 patient to receive a matching placebo orally for 5 consecutive days, starting at the lowest dose for the infecting genotype. Doses were escalated stepwise once adequate safety data had been reviewed from the previous dosing group. Viral load and resistance testing was to be performed daily and every other day, respectively, for the first 10 days of the study and then at 2 weeks, 3 weeks, 1 month, and 2 months after the last dose of elbasvir. The study was conducted in accordance with good clinical practice guidelines. All participants provided written informed consent.

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Viral quantification, sequencing, and resistance analyses. [1]
In the phase 1b study, HCV RNA levels were measured in plasma specimens obtained at baseline, during and at the end of Elbasvir monotherapy, and at periodic follow-up visits by the TaqMan 2.0 assay with lower limits of quantification and detection of 25 and 9.3 IU/ml, respectively. Blood samples were also collected for viral resistance testing at prespecified time points, including prior to the first elbasvir dose, near the nadir of the HCV RNA level, and up to 2 months after the last elbasvir dose provided that the HCV RNA level remained >1,000 IU/ml. [1]
The full-length NS5A gene was amplified from plasma samples using RT-PCR followed by population and selective clonal sequencing. Due to the sensitivity of the assay, resistance analyses were routinely performed only on samples with HCV RNA levels of >1,000 IU/ml. The resultant amino acid sequences were compared to genotype 1a (H77; GenBank no. NC_004102), genotype 1b (con1; GenBank no. AJ238799), or genotype 3 (S52; GenBank no. GU814263) referents. The limit of variant detection in population sequencing was presumed to be ∼20 to 25% of the viral quasispecies. Polymorphisms identified in ≥10% of patients were selected for more detailed analysis. For clonal sequencing, amino acids 1 to 448 of NS5A were amplified by RT-PCR, and the resultant amplicons were cloned into a TOPO TA vector. Approximately 40 clones were sequenced at each time point. Polymorphisms detected in more than a single clone were included in the analysis. [1]
In phenotypic analyses to determine the antiviral potency of Elbasvir against detected variants, genotype-specific replicons were constructed to incorporate NS5A polymorphisms. The shift (n-fold) in elbasvir EC for each variant replicon was expressed relative to the EC for the corresponding wild-type replicon. The fitness of resistant variants was evaluated by comparing colony counts to a wild-type referent.

Absorption, Distribution and Excretion
Elbasvir reaches peak plasma concentration 3-6 hours after administration and has an absolute bioavailability of 32%. When co-administered with food, the peak concentration of elbasvir increases 1.5-fold, but this increase in exposure is not likely to be clinically relevant.
Elbasvir is mainly eliminated in the feces (90%) with very little eliminated in the urine (<1%).
Elbasvir has an estimated apparent volume of distribution of 680 liters. It is thought to distribute into most tissues including the liver.
The clearance of elbasvir has not been determined.

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Metabolism / Metabolites
Elbasvir is partially eliminated by oxidative metabolism meditated by CYP3A. No circulating metabolites of elbasvir have been detected in human plasma.

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Biological Half-Life
The geometric mean apparent terminal half-life for elbasvir is 24 hours in HCV-infected subjects.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Elbasvir has not been studied in nursing mothers being treated for hepatitis C infection. Because it is greater than 99.9% bound to maternal plasma proteins, amounts in breastmilk are likely to be very low. Some sources recommend against breastfeeding when elbasvir is used with ribavirin.
Hepatitis C is not transmitted through breastmilk and breastmilk has been shown to inactivate hepatitis C virus (HCV). However, the Centers for Disease Control recommends that mothers with HCV infection should consider abstaining from breastfeeding if their nipples are cracked or bleeding. It is not clear if this warning would apply to mothers who are being treated for hepatitis C.
Infants born to mothers with HCV infection should be tested for HCV infection; because maternal antibody is present for the first 18 months of life and before the infant mounts an immunologic response, nucleic acid testing is recommended.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Elbasvir is more than 99.9% bound to plasma proteins. It binds both human serum albumin and α1-acid glycoprotein.

[1]. Susceptibilities of genotype 1a, 1b, and 3 hepatitis C virus variants to the NS5A inhibitor Elbasvir. Antimicrob Agents Chemother. 2015 Nov;59(11):6922-6929.

[2]. The Combination of Grazoprevir, a Hepatitis C Virus (HCV) NS3/4A Protease Inhibitor, and Elbasvir, an HCV NS5A Inhibitor, Demonstrates a High Genetic Barrier to Resistance in HCV Genotype 1a Replicons. Antimicrob Agents Chemother. 2016 A.

Pharmacodynamics
Elbasvir is classified as a direct-acting antiviral (DAA) and prevents viral replication in HCV genotypes 1a, 1b, and 4.

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Elbasvir is a complex organic heterotetracyclic compound that is a hepatitis C virus nonstructural protein 5A inhibitor used in combination with grazoprevir (under the brand name Zepatier) for treatment of chronic HCV genotypes 1 or 4 infection in adults. It has a role as an antiviral drug, a hepatoprotective agent and a hepatitis C virus nonstructural protein 5A inhibitor. It is a L-valine derivative, a member of imidazoles, a carbamate ester, a N-acylpyrrolidine, an organic heterotetracyclic compound and a ring assembly.
Elbasvir is a direct-acting antiviral medication used as part of combination therapy to treat chronic hepatitis C, an infectious liver disease caused by infection with hepatitis C virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, affecting 72% of all chronic HCV patients. Treatment options for chronic hepatitis C have advanced significantly since 2011, with the development of direct-acting antivirals (DAAs) such as elbasvir. Elbasvir is an inhibitor of NS5A, a protein essential for viral replication and virion assembly.[synthesis] The barrier to the development of resistance to NS5A inhibitors is lower than that of NS5B inhibitors, another class of DAAs. Substitutions at amino acid positions 28, 30, 31, or 93 are known to confer resistance to elbasvir. Despite this disadvantage elbasvir is still effective against HCV, particularly when paired with [grazoprevir]. Elbasvir is available as a fixed-dose combination product with [grazoprevir] (tradename: Zepatier) used for the treatment of chronic hepatitis C. Approved in January 2016 by the FDA, Zepatier is indicated for the treatment of HCV genotypes 1 and 4 with or without [ribavirin] depending on the presence of resistance-associated amino acid substitutions in the NS5A protein and previous treatment failure with [ribavirin], [peginterferon alfa-2a], [peginterferon alfa-2b], or other NS3/4A inhibitors like [boceprevir], [simeprevir], or [telaprevir]. Elbasvir and [grazoprevir] are used with or without [ribavirin] with the intent to cure, or achieve a sustained virologic response (SVR), and have been shown to achieve a SVR between 94% and 97% for genotype 1 and 97% and 100% for genotype 4 after 12 weeks of treatment.. SVR and eradication of HCV 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. In a computational target-based drug repurposing investigation published in April 2020, elbasvir was predicted to bind stably and preferentially to three proteins necessary for viral replication of SARS-CoV-2, the human coronavirus responsible for the COVID-19 pandemic. While these results are suggestive of antiviral efficacy, follow-up clinical trials are required to validate elbasvir as a potential therapy against SARS-CoV-2.

Elbasvir is a Hepatitis C Virus NS5A Inhibitor. The mechanism of action of elbasvir is as a Breast Cancer Resistance Protein Inhibitor.
Elbasvir is a small molecule drug with a maximum clinical trial phase of IV (across all indications) that was first approved in 2016 and is indicated for viral disease and chronic hepatitis c virus infection and has 2 investigational indications.

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Elbasvir is an investigational NS5A inhibitor with in vitro activity against multiple HCV genotypes. Antiviral activity of elbasvir was measured in replicons derived from wild-type or resistant variants of genotypes 1a, 1b, and 3. The barrier to resistance was assessed by the number of resistant colonies selected by exposure to various elbasvir concentrations. In a phase 1b dose-escalating study, virologic responses were determined in 48 noncirrhotic adult men with chronic genotype 1 or 3 infections randomized to placebo or elbasvir from 5 to 50 mg (genotype 1) or 10 to 100 mg (genotype 3) once daily for 5 days. The NS5A gene was sequenced from plasma specimens obtained before, during, and after treatment. Elbasvir suppressed the emergence of resistance-associated variants (RAVs) in vitro in a dose-dependent manner. Variants selected by exposure to high elbasvir concentrations typically encoded multiple amino acid substitutions (most commonly involving loci 30, 31, and 93), conferring high-level elbasvir resistance. In the monotherapy study, patients with genotype 1b had greater reductions in HCV RNA levels than patients with genotype 1a at all elbasvir doses; responses in patients with genotype 3 were generally less pronounced than for genotype 1, particularly at lower elbasvir doses. M28T, Q30R, L31V, and Y93H in genotype 1a, L31V and Y93H in genotype 1b, and A30K, L31F, and Y93H in genotype 3 were the predominant RAVs selected by elbasvir monotherapy. Virologic findings in patients were consistent with the preclinical observations. NS5A-RAVs emerged most often at amino acid positions 28, 30, 31, and 93 in both the laboratory and clinical trial. (The MK-8742 P002 trial has been registered at ClinicalTrials.gov under identifier NCT01532973.).[1]

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The selection of resistance-associated variants (RAVs) against single agents administered to patients chronically infected with hepatitis C virus (HCV) necessitates that direct-acting antiviral agents (DAAs) targeting multiple viral proteins be developed to overcome failure resulting from emergence of resistance. The combination of grazoprevir (formerly MK-5172), an NS3/4A protease inhibitor, and Elbasvir (formerly MK-8742), an NS5A inhibitor, was therefore studied in genotype 1a (GT1a) replicon cells. Both compounds were independently highly potent in GT1a wild-type replicon cells, with 90% effective concentration (EC90) values of 0.9 nM and 0.006 nM for grazoprevir and elbasvir, respectively. No cross-resistance was observed when clinically relevant NS5A and NS3 RAVs were profiled against grazoprevir and elbasvir, respectively. Kinetic analyses of HCV RNA reduction over 14 days showed that grazoprevir and elbasvir inhibited prototypic NS5A Y93H and NS3 R155K RAVs, respectively, with kinetics comparable to those for the wild-type GT1a replicon. In combination, grazoprevir and elbasvir interacted additively in GT1a replicon cells. Colony formation assays with a 10-fold multiple of the EC90 values of the grazoprevir-elbasvir inhibitor combination suppressed emergence of resistant colonies, compared to a 100-fold multiple for the independent agents. The selected resistant colonies with the combination harbored RAVs that required two or more nucleotide changes in the codons. Mutations in the cognate gene caused greater potency losses for elbasvir than for grazoprevir. Replicons bearing RAVs identified from resistant colonies showed reduced fitness for several cell lines and may contribute to the activity of the combination. These studies demonstrate that the combination of grazoprevir and elbasvir exerts a potent effect on HCV RNA replication and presents a high genetic barrier to resistance. The combination of grazoprevir and elbasvir is currently approved for chronic HCV infection.[2]

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Elbasvir plus grazoprevir (an investigational NS3/4A protease inhibitor) as a once-daily, oral, single fixed-dose combination tablet is currently being developed for treatment of chronic HCV infection. Further analyses of the phase 3 trials of grazoprevir-elbasvir will soon provide more critical data concerning the safety and efficacy of this novel double direct-acting antiviral combination.[1]

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Collectively, these results demonstrate that the combination of grazoprevir, an NS3/4A inhibitor, and Elbasvir, an NS5A inhibitor, potently inhibits HCV RNA synthesis, with no evidence of antagonism, and present a high genetic barrier to resistance. The inhibitor combination presents an attractive alternative as an oral, interferon-free DAA for patients chronically infected with HCV. In recent clinical studies, the in vitro activities translated to robust clinical efficacy for the combination. In treatment-naive GT1a patients given a once-daily dose of 50 mg/100 mg elbasvir-grazoprevir, an SVR rate of 95% was achieved in patients. The RAVs and dominant resistance pathways observed in clinical studies of GT1a-infected subjects largely mirrored what was observed in vitro. The most common treatment-emergent (TE) NS5A RAV in virologic failures was at Q30. Similarly, D168 amino acid substitutions accounted for most TE NS3 RAVs in virologic failures. The combination has been approved (January 2016) for the treatment of chronic HCV infections.[2]

C49H55N9O7

882.02

881.422

C, 66.72; H, 6.29; N, 14.29; O, 12.70

1370468-36-2

71661251

White to yellow solid powder

1.4±0.1 g/cm3

1.701

6.98

4

9

13

65

1680

5

O=C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C(=O)OC([H])([H])[H])N1C([H])([H])C([H])([H])C([H])([H])C1([H])C1=NC([H])=C(C2C([H])=C([H])C3=C(C=2[H])C([H])=C2C4C([H])=C([H])C(=C([H])C=4O[C@@]([H])(C4C([H])=C([H])C([H])=C([H])C=4[H])N23)C2=C([H])N=C([C@]3([H])C([H])([H])C([H])([H])C([H])([H])N3C([C@]([H])(C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C(=O)OC([H])([H])[H])=O)N2[H])N1[H]

BVAZQCUMNICBAQ-PZHYSIFUSA-N

InChI=1S/C49H55N9O7/c1-27(2)41(54-48(61)63-5)45(59)56-20-10-14-37(56)43-50-25-34(52-43)30-17-19-36-32(22-30)23-39-33-18-16-31(24-40(33)65-47(58(36)39)29-12-8-7-9-13-29)35-26-51-44(53-35)38-15-11-21-57(38)46(60)42(28(3)4)55-49(62)64-6/h7-9,12-13,16-19,22-28,37-38,41-42,47H,10-11,14-15,20-21H2,1-6H3,(H,50,52)(H,51,53)(H,54,61)(H,55,62)/t37-,38-,41-,42-,47-/m0/s1

methyl N-[(2S)-1-[(2S)-2-[5-[(6S)-3-[2-[(2S)-1-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]pyrrolidin-2-yl]-1H-imidazol-5-yl]-6-phenyl-6H-indolo[1,2-c][1,3]benzoxazin-10-yl]-1H-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate

Elbasvir; Zepatier; MK8742; MK 8742; Elbasvir; 1370468-36-2; Elbasvir [USAN]; Elbasvir [USAN:INN]; UNII-632L571YDK; 632L571YDK; MK-8742

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (2.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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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 (Please use freshly prepared in vivo formulations for optimal results.)