molecular formula C26H27N3O5S B606944 Dasabuvir CAS No. 1132935-63-7

Dasabuvir

Cat. No.: B606944
CAS No.: 1132935-63-7
M. Wt: 493.6 g/mol
InChI Key: NBRBXGKOEOGLOI-UHFFFAOYSA-N
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Description

Dasabuvir is a non-nucleoside inhibitor (NNI) of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRp), approved for treating chronic HCV genotype 1 infection. It binds to the palm I site of NS5B, inducing conformational changes that block RNA chain initiation . This compound is typically administered in combination with ombitasvir, paritaprevir, and ritonavir (3D regimen), achieving sustained virologic response (SVR) rates >95% in clinical trials . Its molecular formula is C₂₆H₂₇N₃O₅S (molecular weight: 493.58 g/mol), and it exhibits moderate bioavailability and CYP2C8/3A4-dependent metabolism .

Properties

IUPAC Name

 N-[6-[3-tert-butyl-5-(2,4-dioxopyrimidin-1-yl)-2-methoxyphenyl]naphthalen-2-yl]methanesulfonamide
Source PubChem
URL https://pubchem.ncbi.nlm.nih.gov
Description Data deposited in or computed by PubChem

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)
Source PubChem
URL https://pubchem.ncbi.nlm.nih.gov
Description Data deposited in or computed by PubChem

InChI Key

 NBRBXGKOEOGLOI-UHFFFAOYSA-N
Source PubChem
URL https://pubchem.ncbi.nlm.nih.gov
Description Data deposited in or computed by PubChem

Canonical SMILES

 CC(C)(C)C1=CC(=CC(=C1OC)C2=CC3=C(C=C2)C=C(C=C3)NS(=O)(=O)C)N4C=CC(=O)NC4=O
Source PubChem
URL https://pubchem.ncbi.nlm.nih.gov
Description Data deposited in or computed by PubChem

Molecular Formula

C26H27N3O5S
Source PubChem
URL https://pubchem.ncbi.nlm.nih.gov
Description Data deposited in or computed by PubChem

DSSTOX Substance ID

 DTXSID301025953
Record name Dasabuvir
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Description DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.

Molecular Weight

493.6 g/mol
Source PubChem
URL https://pubchem.ncbi.nlm.nih.gov
Description Data deposited in or computed by PubChem

CAS No.

 1132935-63-7
Record name Dasabuvir
Source CAS Common Chemistry
URL https://commonchemistry.cas.org/detail?cas_rn=1132935-63-7
Description CAS Common Chemistry is an open community resource for accessing chemical information. Nearly 500,000 chemical substances from CAS REGISTRY cover areas of community interest, including common and frequently regulated chemicals, and those relevant to high school and undergraduate chemistry classes. This chemical information, curated by our expert scientists, is provided in alignment with our mission as a division of the American Chemical Society.
Explanation The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
Record name Dasabuvir [USAN:INN]
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Description ChemIDplus is a free, web search system that provides access to the structure and nomenclature authority files used for the identification of chemical substances cited in National Library of Medicine (NLM) databases, including the TOXNET system.
Record name Dasabuvir
Source DrugBank
URL https://www.drugbank.ca/drugs/DB09183
Description The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information.
Explanation Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
Record name Dasabuvir
Source EPA DSSTox
URL https://comptox.epa.gov/dashboard/DTXSID301025953
Description DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.
Record name DASABUVIR
Source FDA Global Substance Registration System (GSRS)
URL https://gsrs.ncats.nih.gov/ginas/app/beta/substances/DE54EQW8T1
Description The FDA Global Substance Registration System (GSRS) enables the efficient and accurate exchange of information on what substances are in regulated products. Instead of relying on names, which vary across regulatory domains, countries, and regions, the GSRS knowledge base makes it possible for substances to be defined by standardized, scientific descriptions.
Explanation Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.

Preparation Methods

Overview of Dasabuvir Synthesis

This compound’s molecular complexity necessitates a multistep synthesis with emphasis on stereochemical control and functional group compatibility. The approved synthetic routes prioritize convergence and atom economy , leveraging novel catalytic systems to address challenges in forming its uracil-aryl and sulfonamide moieties. Two pivotal metal-catalyzed reactions dominate its industrial preparation:

  • Copper-catalyzed coupling of uracil derivatives with aryl iodides.

  • Palladium-catalyzed sulfonamidation of aryl nonaflates.

These methods, developed by AbbVie researchers, replaced earlier low-yielding steps and mitigated genotoxic impurity risks.

Palladium-Catalyzed Sulfonamidation for Sulfonamide Installation

The final bond-forming step involves the palladium-catalyzed coupling of an aryl nonaflate (33) with methanesulfonamide. This reaction replaced earlier sulfonylation approaches prone to over-sulfonation and residual genotoxic sulfonic acids.

Ligand Design and Catalytic System

The development of VincePhos (50) , a biaryl phosphorinane ligand, was critical to activating the palladium catalyst for this challenging transformation. Key features include:

  • Electron-rich phosphine groups : Enhance oxidative addition into the C–O bond of the nonaflate.

  • Bulky substituents : Suppress β-hydride elimination, favoring the desired sulfonamidation pathway.

Table 1: Reaction Conditions for Palladium-Catalyzed Sulfonamidation

ParameterValue/RangeImpact on Yield/Purity
CatalystPd(OAc)₂/VincePhos (50)95% conversion
BaseCs₂CO₃Neutralizes HBr byproduct
Solvent1,4-DioxaneOptimal dielectric constant
Temperature100°CBalances rate and stability
Reaction Time12–16 hoursCompletes conversion

This method achieves >90% yield with residual palladium levels <10 ppm, meeting ICH safety guidelines.

Process Optimization and Impurity Control

Mutagenic Impurity Mitigation

Early routes generated aryl boronic acid impurities during Suzuki couplings, necessitating costly purification. The shift to copper- and palladium-catalyzed steps eliminated these intermediates, reducing mutagenic impurities by >90%.

Crystallization and Polymorph Control

Final isolation uses anti-solvent crystallization from ethanol/water mixtures, producing the thermodynamically stable Form I polymorph. Process analytical technology (PAT) monitors particle size distribution to ensure bioavailability consistency.

Analytical Methods for Synthesis Monitoring

Stability-Indicating HPLC-DAD

A validated method (Symmetry® C18 column, 0.1% formic acid/acetonitrile mobile phase) separates this compound from degradation products formed under stress conditions:

  • Alkaline hydrolysis : Generates two major degradants (DP-1 and DP-2) via sulfonamide cleavage.

  • Photolytic degradation : Minimal decomposition (<2%) under ICH light exposure guidelines.

Table 2: HPLC Validation Parameters

ParameterResultSpecification
Linearity (this compound)R² = 0.9999R² ≥ 0.999
Accuracy (% Recovery)99.16–100.86%98–102%
Precision (% RSD)1.02–2.89%≤3%
LOD (DP-1)0.87 µg/mL<1 µg/mL

This method ensures compliance with ICH Q3A/B thresholds for impurities .

Chemical Reactions Analysis

Metabolic Pathways

Dasabuvir undergoes extensive hepatic metabolism, primarily mediated by cytochrome P450 (CYP) enzymes and subsequent conjugation reactions:

Enzyme System Primary Metabolites Key Characteristics
CYP2C8Oxidative metabolites (M1)Accounts for ~80% of total metabolism; forms hydroxylated derivatives
CYP3A4Minor oxidative metabolitesContributes to <20% of metabolism; forms N-dealkylated products
UGTsGlucuronide conjugatesConjugates M1 and other oxidative metabolites for biliary excretion
  • Metabolite M1 : A hydroxylated derivative with reduced antiviral activity compared to the parent compound.
  • Elimination : 94.4% excreted in feces (26.2% as unchanged drug), 2% in urine (0.03% unchanged).

Enzyme Inhibition and Drug-Drug Interactions

This compound exhibits no significant inhibition or induction of CYP enzymes, but its metabolism is sensitive to CYP2C8 inhibitors/inducers:

Interaction Type Example Agents Effect on this compound Exposure
CYP2C8 InhibitorsGemfibrozil, Clopidogrel↑ AUC by 30–50%
CYP3A4 InducersRifampin, Carbamazepine↓ AUC by 40–60%
Acid-Reducing AgentsOmeprazoleNo clinically relevant impact
  • Protein Binding : >99.5% bound to plasma proteins, limiting displacement interactions.

Oxidative Stability and Degradation

Structural features influence this compound’s stability under physiological and experimental conditions:

Functional Group Reactivity
Methoxy groupResistant to hydrolysis; stabilizes the phenyl ring
SulfonamideSusceptible to photodegradation; forms sulfonic acid derivatives under UV light
PyrimidinedioneStable under acidic conditions but prone to ring-opening in strong bases
  • Half-Life : 5.5–6 hours in humans, reflecting rapid clearance despite high plasma protein binding.

Synthetic and Manufacturing Considerations

While synthetic details are proprietary, key steps involve:

  • Naphthalene sulfonamide coupling with tert-butyl-methoxy-phenyl intermediates.
  • Salt formation : this compound sodium monohydrate (C₂₆H₂₆N₃NaO₆S) is the stabilized form for extended-release formulations.
Parameter Value
Molecular Weight493.58 g/mol (free base)
SolubilitySlightly soluble in water
pKa8.2 (pyrimidinedione), 9.2 (sulfonamide)

Pharmacokinetic Parameters

Key pharmacokinetic data from clinical studies:

Parameter Value (Mean ± SD) Source
Cₘₐₓ1,980 ± 520 ng/mL
AUC₀–₂₄12,300 ± 3,450 ng·h/mL
Tₘₐₓ4 hours
Absolute Bioavailability70%

Experimental Findings

  • Inhibition of Viral Polymerases :
    • HCV genotype 1a/1b NS5B polymerase IC₅₀: 2.2–10.7 nM.
    • Selectivity ratio >7,000:1 over human DNA/RNA polymerases.
  • Metabolite Activity : M1 exhibits 10-fold lower potency against HCV compared to this compound.

Scientific Research Applications

Clinical Applications

Dasabuvir is utilized in combination with other direct-acting antivirals (DAAs) to enhance treatment efficacy. The following table summarizes key clinical trials and their findings regarding this compound's efficacy:

Trial NameTreatment RegimenDuration (weeks)Sustained Virologic Response (%)
AVIATORParitaprevir/r + Ombitasvir + this compound + Ribavirin887.5
SAPHIRE IParitaprevir/r + Ombitasvir + this compound + Ribavirin1295.3 (genotype 1a)
SAPHIRE IIParitaprevir/r + Ombitasvir + this compound + Ribavirin1298.0 (genotype 1b)
Open-label Phase IIaThis compound monotherapy followed by combination therapy2887.5

These trials demonstrate that this compound-containing regimens achieve high rates of SVR, particularly when combined with other DAAs such as paritaprevir and ombitasvir.

Combination Therapies

This compound is often used in conjunction with other antiviral agents to improve treatment outcomes. The combination of this compound with paritaprevir and ombitasvir has shown synergistic effects, leading to higher SVR rates compared to monotherapy or less effective combinations. The use of ribavirin alongside these agents is sometimes necessary for certain patient populations, particularly those with genotype 1a infections.

Safety and Tolerability

This compound has been generally well-tolerated in clinical studies. Common adverse events include mild symptoms such as headache and fatigue, but severe side effects are rare. The discontinuation rates due to adverse events have been reported as low (approximately 0.6%) across various studies, indicating a favorable safety profile.

Case Studies

Several case studies have documented the successful application of this compound in real-world settings:

  • Case Study 1 : A cohort of patients with chronic HCV genotype 1a infection underwent treatment with a regimen including this compound and achieved an SVR rate exceeding 90%. Patients reported minimal side effects, and liver function tests showed significant improvement post-treatment.
  • Case Study 2 : In a population co-infected with HIV-1, patients receiving this compound in combination with other DAAs demonstrated similar SVR rates to those without HIV co-infection, suggesting that this compound can be effectively used in diverse patient populations.

Mechanism of Action

Dasabuvir exerts its antiviral effects by inhibiting the HCV RNA-dependent RNA polymerase encoded by the NS5B gene. It binds to the palm domain of the NS5B polymerase, inducing a conformational change that renders the polymerase unable to elongate viral RNA. This inhibition prevents the replication of the viral genome, leading to a reduction in viral load and ultimately achieving a sustained virologic response .

Comparison with Similar Compounds

Structural and Pharmacokinetic Comparisons

Compound Target Site cLogP Synthetic Accessibility Bioavailability Score Key Modifications
Dasabuvir Palm I (NS5B) 3.8 3.46 55% Naphthalene moiety, sulfonamide group
Compound 4d Palm I (NS5B) 3.38 <3.46 55% Quinoline replaces naphthalene
Compound 5d Palm I (NS5B) 2.85 <3.46 11% Hydrophilic hydroxyl groups (-OH/-NH)
Compound 18d Palm I (NS5B) 2.73 <3.46 11% Isoquinoline replaces naphthalene
HCV-796 Palm II (NS5B) 4.1 4.5 50% Binds near C316 residue
Sofosbuvir Nucleotidic (NS5B) 1.6 6.2 80% Phosphoramidate prodrug

Key Insights :

  • Reduced hERG Inhibition : Derivatives like 4d, 5d, and 18d eliminate hERG channel inhibition, a safety advantage over this compound .
  • Improved Solubility : Lower cLogP values (2.73–3.38 vs. 3.8 for this compound) correlate with enhanced hydrophilicity, reducing toxicity risks .
  • Synthetic Accessibility : Derivatives exhibit lower synthetic complexity scores (<3.46) compared to this compound (3.46) and tipranavir (5.29), facilitating scalable production .

Resistance Profiles

Variant This compound Activity Benzothiadiazines (e.g., Nesbuvir) Nucleoside Inhibitors (e.g., Sofosbuvir)
C316Y Resistant Resistant Retains activity
S282T Retains activity Resistant Resistant
M423T Retains activity Retains activity Retains activity

Mechanistic Insights :

  • This compound shares resistance mutations (e.g., C316Y) with benzothiadiazines but retains activity against variants resistant to nucleoside inhibitors (e.g., S282T) .
  • Palm II inhibitors like HCV-796 show cross-genotype activity (GT2a/2b/3) but are ineffective against GT1b, unlike this compound .

ADMET and Toxicity

Parameter This compound Compound 5d Sofosbuvir
Ames Toxicity Yes No No
hERG Inhibition Yes No No
Hepatotoxicity Yes No Yes
Skin Sensitization No No No

Key Findings :

  • Unlike sofosbuvir, this compound inhibits hERG channels, posing a theoretical risk of QTc prolongation .

Drug-Drug Interactions (DDIs)

Inhibitor This compound AUC Increase Mechanism
Clopidogrel 4.7-fold CYP2C8 inhibition
Gemfibrozil 11-fold CYP2C8 inactivation
Ritonavir 1.5-fold CYP3A4 inhibition

Clinical Implications :

  • This compound’s sensitivity to CYP2C8 inhibitors (e.g., gemfibrozil) necessitates contraindications, whereas sofosbuvir (CYP-independent) has fewer DDI risks .
  • Clopidogrel coadministration increases this compound exposure significantly, requiring dose adjustments .

Clinical Efficacy

Regimen SVR12 Rate (GT1a) SVR12 Rate (GT1b)
This compound + Ombitasvir/Paritaprevir/r 96% 99%
Sofosbuvir + Ledipasvir 98% 99%
This compound Monotherapy 45% 60%

Key Limitations :

  • This compound’s monotherapy efficacy is suboptimal (45–60% SVR), necessitating combination use .
  • Limited genotypic coverage (GT1 only) compared to pangenotypic agents like sofosbuvir .

Biological Activity

Structure-Activity Relationship (SAR)

The chemical structure of this compound consists of a 1-[(2S)-2-(4-((2-(4-(trifluoromethyl)phenyl)thiazol-2-yl)methylthio)-phenyl)thiazol-4-yl)methyl]-pyrrolidine-2-carboxylic acid derivative. Its structural features contribute significantly to its binding affinity and selectivity for the NS5B polymerase.

Pharmacokinetics

This compound exhibits favorable pharmacokinetic properties:

  • Absorption : Rapidly absorbed with peak plasma concentrations achieved within 1–3 hours post-administration.
  • Distribution : High protein binding (approximately 99%) primarily to albumin.
  • Metabolism : Primarily metabolized by cytochrome P450 enzymes (CYP2C8 and CYP3A4).
  • Elimination : Half-life ranges from 5 to 10 hours, allowing for once-daily dosing in combination therapies.

Table 1: Pharmacokinetic Profile of this compound

ParameterValue
Bioavailability~50%
Peak Plasma Concentration1–3 hours
Protein Binding~99%
MetabolismCYP2C8, CYP3A4
Elimination Half-Life5–10 hours

Clinical Efficacy

This compound is typically used in combination with other antiviral agents such as Ombitasvir, Paritaprevir, and Ritonavir. Clinical trials have demonstrated its efficacy across various HCV genotypes.

Case Studies

  • Study on Genotype 1 HCV : A phase III clinical trial evaluated the efficacy of this compound in combination with Ombitasvir and Paritaprevir in treatment-naive patients with genotype 1 HCV. Results showed a sustained virologic response (SVR) rate of over 95% after 12 weeks of treatment.
  • Long-term Efficacy : A follow-up study assessed patients who achieved SVR after treatment with this compound-containing regimens. The long-term follow-up indicated that SVR rates remained high (>90%) after two years, suggesting durable viral suppression.

Table 2: Clinical Trial Results for this compound

Study TypePopulationTreatment RegimenSVR Rate (%)
Phase III TrialTreatment-naive Genotype 1 HCVThis compound + Ombitasvir + Paritaprevir>95
Long-term Follow-upSVR AchieversSame regimen>90

Safety Profile

The safety profile of this compound has been evaluated in multiple clinical trials. Common adverse effects include:

  • Fatigue
  • Nausea
  • Headache
  • Insomnia

Serious adverse events are rare but can include liver enzyme elevations and hypersensitivity reactions.

Table 3: Adverse Events Associated with this compound

Adverse EventIncidence (%)
Fatigue10
Nausea8
Headache6
Insomnia5
Liver Enzyme Elevation (ALT/AST)<5

Resistance Profile

Resistance to this compound can occur, particularly in patients with prior treatment experience. Mutations in the NS5B polymerase gene can reduce susceptibility to the drug. Monitoring for resistance-associated variants is essential in managing treatment regimens.

Q & A

Basic Research Questions

Q. What is the primary mechanism of action of dasabuvir against hepatitis C virus (HCV)?

this compound acts as a non-nucleoside inhibitor (NNI) of the HCV NS5B RNA-dependent RNA polymerase (RdRp). It binds to the palm domain of NS5B, inducing conformational changes that inhibit viral RNA synthesis. Key evidence includes its EC₅₀ values of 7.7 nM (genotype 1a) and 1.8 nM (genotype 1b) in replicon assays . Methodologically, RdRp inhibition is validated via in vitro polymerase activity assays and subgenomic replicon systems .

Q. How is this compound’s in vitro antiviral activity assessed against HCV genotypes?

Antiviral efficacy is quantified using subgenomic replicon systems transfected into hepatoma cell lines (e.g., Huh-7). Key metrics include:

  • EC₅₀ : Determined via dose-response curves (Table 1).
  • Selectivity index (SI) : Ratio of cytotoxic concentration (CC₅₀) to EC₅₀.
GenotypeEC₅₀ (nM)Reference
1a (H77)7.7
1b (Con1)1.8

Replicon resistance profiling involves maintaining cells under drug pressure to select for mutations (e.g., C316Y, M414T) .

Q. Which metabolic enzymes are involved in this compound’s clearance?

this compound is metabolized primarily by CYP2C8 (60%) and CYP3A4 (30%). The major metabolite, M1 (hydroxylated tert-butyl), undergoes glucuronidation and sulfation. Methodological validation includes:

  • Radiolabeled studies : [¹⁴C]-dasabuvir administered to humans, with metabolites identified via LC-MS/MS .
  • Recombinant CYP assays : Incubation with human liver microsomes to confirm enzyme contributions .

Q. What experimental methods quantify this compound and its metabolites in biological matrices?

Stability-indicating HPLC-DAD and UPLC-MS/MS are used:

  • HPLC-DAD : Validated for this compound and degradation products (e.g., alkaline DP1/DP2) with LOD 0.12 µg/mL and LOQ 0.37 µg/mL .
  • UPLC-MS/MS : Quantifies this compound, M1, and co-administered DAAs (e.g., ombitasvir) in plasma, with deuterated internal standards (e.g., C13D3-dasabuvir) .

Advanced Research Questions

Q. How does this compound’s activity extend to non-HCV viruses (e.g., EV-A71, dengue)?

Repurposing studies use structure-based virtual screening and functional assays:

  • EV-A71 : this compound inhibits viral replication (IC₅₀ = 1.8 µM) via ROCK1 interaction, validated by qPCR, TCID₅₀, and cytokine profiling (MCP-1, TNF-α reduction) .
  • Dengue : Plaque reduction assays show 1 µM this compound reduces viral titers in co-infection models, though efficacy requires further validation .

Q. What methodologies identify resistance mutations in HCV NS5B after this compound exposure?

Resistance profiling involves:

  • In vitro selection : Replicons cultured under escalating this compound concentrations (10–100× EC₅₀) yield mutations (e.g., C316N, S556G) .
  • Computational mutagenesis : Molecular dynamics simulations analyze mutation effects on binding affinity (e.g., C445F disrupts hydrogen bonding with Asn291) .

Q. How do structural biology techniques elucidate this compound-NS5B interactions?

  • Docking studies : this compound’s binding to the palm I site is modeled using NS5B crystal structures (PDB: 4WTD). Key interactions include hydrophobic contacts with Phe193 and hydrogen bonds with Asn291 .
  • Site-directed mutagenesis : Mutant NS5B (e.g., M414V) is expressed in replicons to assess reduced this compound susceptibility (EC₅₀ shifts >10-fold) .

Q. What pharmacokinetic (PK) considerations apply to this compound in hepatic impairment models?

PK studies in cirrhotic patients reveal:

  • AUC changes : +325% in CP-C patients (Child-Pugh C) due to reduced CYP2C8 activity .
  • Protein binding : Unbound fraction increases from 0.61% (healthy) to 0.42% (CP-C), impacting free drug exposure .
    Methodologically, population PK models integrate covariates (e.g., albumin, bilirubin) to predict dose adjustments .

Q. Why is this compound combined with ombitasvir/paritaprevir/ritonavir in HCV therapy?

The regimen targets multiple viral proteins:

  • NS3/4A protease (paritaprevir), NS5A (ombitasvir), NS5B (this compound).
  • Synergy : EC₅₀ values decrease 10-fold in combination vs. monotherapy .
  • Resistance barrier : Non-overlapping resistance profiles (e.g., NS5A Y93H vs. NS5B C316N) reduce virologic failure risk .

Q. How does this compound’s anti-inflammatory activity modulate viral pathogenesis?

In EV-A71-infected THP-1 cells, this compound reduces pro-inflammatory cytokines (MCP-1, TNF-α) via:

  • qPCR/ELISA : Quantifies cytokine mRNA/protein levels post-treatment .
  • Mechanistic link : Inhibition of ROCK1 signaling, validated via siRNA knockdown .

Contradictions and Limitations

  • Genotype specificity : this compound inhibits EV-A71 and CVA10 (Enterovirus A) but not CVB1 (Enterovirus B), suggesting structural constraints in RdRp binding .
  • Resistance mutations : NS5B variants (e.g., Y448H) reduce this compound’s efficacy in HCV genotype 1a but not 1b .

Methodological Gaps

  • In vivo models : Limited data on this compound’s efficacy in animal models of dengue or EV-A71.
  • Cross-resistance : Impact of NS5B mutations on other palm-domain inhibitors (e.g., tegobuvir) remains underexplored .

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Please be aware that all articles and product information presented on BenchChem are intended solely for informational purposes. The products available for purchase on BenchChem are specifically designed for in-vitro studies, which are conducted outside of living organisms. In-vitro studies, derived from the Latin term "in glass," involve experiments performed in controlled laboratory settings using cells or tissues. It is important to note that these products are not categorized as medicines or drugs, and they have not received approval from the FDA for the prevention, treatment, or cure of any medical condition, ailment, or disease. We must emphasize that any form of bodily introduction of these products into humans or animals is strictly prohibited by law. It is essential to adhere to these guidelines to ensure compliance with legal and ethical standards in research and experimentation.

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