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Chemical Structure| 1365970-03-1 Chemical Structure| 1365970-03-1

Structure of Glecaprevir
CAS No.: 1365970-03-1

Chemical Structure| 1365970-03-1

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Glecaprevir is a NS 3/4A inhibitor potentially for the treatment of HCV.

Synonyms: ABT-493; A-1282576

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Product Citations

Product Citations

Shah, Rajiv Nagin ;

Abstract: Hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide with an estimated 58 million suffering with chronic infection and approximately 1.5 million new infections occurring each year. The World Health Organization (WHO) has set ambitious goals to eliminate viral hepatitis by 2030. A key strategy behind these goals is the discovery of Direct Acting (DAAs), which have revolutionised the treatment of infection. However most clinical trials and real world DAA treatment programs have been conducted in high income countries where the predominant circulating -genotypes are epidemic lineages. However, in Sub-Saharan Africa endemic lineages are more common and less well characterised. There is also growing evidence that certain sub genotypes are more challenging to treat, for example sub-genotypes 1l and 4r.The aims of this thesis were to explore the diversity of using datasets from Uganda and Benin. Furthermore, the prevalence of and associated liver disease from people who inject drugs (PWID) in Coastal Kenya was assessed and genetic data was used to explore PWID networks and estimate the origin of in this community. We found highly divergent genomes in Uganda and Benin including the discovery of multiple new subtypes (1q, 1r, 1s and 2xa in Benin and 4xa in Uganda) as well as numerous subtypes that have previously been uncharacterised. Interestingly, we found only epidemic lineages 1a and 4a in Kenyan PWID. Molecular clock analysis suggests the introduction of 1afrom Europe into Kenyan PWID, as recently as 2001, whereas 4a is likely to have been introduced around 1980, from Egypt. Network analysis using genetic data suggests that Kenyan PWID networks are very closely linked, with repeated transmissions between individuals likely. The prevalence of chronic infection in Kenyan PWID is high at 36%, of which 62% were viraemic. Among the 34% of PWID that had HCV-HIV coinfection, 76% were viraemic. The prevalence of baseline NS5A RASs in diverse sub-genotypes from Uganda and Benin is high compared to 1a and 4a seen in Kenyan PWID. However, in vitroexperiments using a sub-genomic replicon system suggest that genotype 2 from Benin is largely susceptible to DAAs. Data from this thesis supports the WHO’s ambitious goals to achieve an 80% in incident infections worldwide by 2030 using appropriate DAA regimens.

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Product Details of Glecaprevir

CAS No. :1365970-03-1
Formula : C38H46F4N6O9S
M.W : 838.87
SMILES Code : O=C(N[C@@]1(C(NS(=O)(C2(C)CC2)=O)=O)[C@@H](C1)C(F)F)[C@H]3N4C[C@@]([H])(C3)OC5=NC6=CC=CC=C6N=C5C(/C=C/CO[C@]7([C@]([H])(OC(N[C@H](C4=O)C(C)(C)C)=O)CCC7)[H])(F)F
Synonyms :
ABT-493; A-1282576
MDL No. :MFCD30533436

Safety of Glecaprevir

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
MT4 cells 59,000 nM Evaluation of cytotoxicity of Glecaprevir in MT4 cells PMC5740381
HepG2 cells 62,000 nM Evaluation of cytotoxicity of Glecaprevir in HepG2 cells PMC5740381
A549-hACE2 cells >94 μM 46 to 50 hours Evaluate the inhibitory effect of Glecaprevir on SARS-CoV-2 in A549-hACE2 cells, no EC50 was determined due to antiviral activity of DMSO at high inhibitor concentrations PMC8370243
Vero E6 cells >178 μM 46 to 50 hours Evaluate the inhibitory effect of Glecaprevir on SARS-CoV-2, results showed low potency PMC8370243
MDCK cells 0.1, 1, 10, 100 µM 48 hours Evaluate the cytotoxicity and antiviral activity of Glecaprevir on MDCK cells. Results showed that Glecaprevir significantly reduced cell activity at 100 µM concentration with a CC50 of 77.32 µM. PMC11818416
Huh-7 cells 0.21 to 4.6 nM Evaluation of antiviral activity of Glecaprevir against HCV replicons of different genotypes PMC5740381

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
BALB/c mice H1N1-UI182 influenza virus infection model Oral 10, 20, 40 mg/kg Once daily for 14 days Evaluate the therapeutic effect of Glecaprevir on H1N1-UI182 influenza virus-infected mice. Results showed that Glecaprevir significantly improved the survival rate of infected mice (80% protection rate) and alleviated lung pathological damage. PMC11818416

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.19mL

0.24mL

0.12mL

5.96mL

1.19mL

0.60mL

11.92mL

2.38mL

1.19mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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