Ruzasvir
Based on 1 Customer Validation
Ruzasvir (MK-8408) is a potent, pan-genotype HCV NS5A inhibitor that blocks RNA synthesis, replication, and assembly. Ruzasvir produces additive to synergistic antiviral effects with Bemnifosbuvir (HY-137958A), Grazoprevir (HY-15298), or Uprifosbuvir (HY-103487) analogs, with no antagonism. Ruzasvir can be used for research on HCV infection.
For research use only. We do not sell to patients.
- Purity : 98.15%
- CAS No.: 1613081-64-3
- Formula: C49H55FN10O7S
- Molecular Weight:947.09
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
All DNA/RNA Synthesis Isoforms
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Biological Activity
Description
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| Huh-7 | EC90 |
0.003 nM
|
Inhibition of HCV GT1a replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
Inhibition of HCV GT1a replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
|
27808515 |
| Huh-7 | EC90 |
0.016 nM
|
Inhibition of HCV GT1a L31V replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
Inhibition of HCV GT1a L31V replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
|
27808515 |
| Huh-7 | EC90 |
0.067 nM
|
Inhibition of HCV GT1a Y93H replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
Inhibition of HCV GT1a Y93H replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
|
27808515 |
| Huh-7 | EC90 |
0.036 nM
|
Inhibition of HCV GT2b(31M) replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
Inhibition of HCV GT2b(31M) replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
|
27808515 |
| Huh-7 | EC90 |
0.007 nM
|
Inhibition of HCV GT3a replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
Inhibition of HCV GT3a replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
|
27808515 |
| Huh-7 | EC90 |
0.009 nM
|
Inhibition of HCV NS5A Y93H variant replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
Inhibition of HCV NS5A Y93H variant replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
|
27808515 |
| Huh-7 | EC90 |
0.011 nM
|
Inhibition of HCV NS5A Q30R variant replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
Inhibition of HCV NS5A Q30R variant replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
|
27808515 |
| Huh-7 | EC90 |
0.002 nM
|
Inhibition of HCV NS5A Y93C variant replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
Inhibition of HCV NS5A Y93C variant replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
|
27808515 |
| Huh-7 | EC90 |
0.001 nM
|
Inhibition of HCV GT2a replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
Inhibition of HCV GT2a replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
|
27808515 |
| Huh-7 | EC90 |
0.006 nM
|
Inhibition of HCV GT3a replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
Inhibition of HCV GT3a replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
|
27808515 |
| Huh-7 | EC90 |
0.027 nM
|
Inhibition of HCV GT6d replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
Inhibition of HCV GT6d replicon replication in Huh-7 derived cells assessed by decreased luciferase signal.
|
27808515 |
| Huh-7 | EC50 |
1 pM
|
Antiviral activity against HCV genotype 1a in human Huh-7 replicon cells assessed as EC50 by replicon assay.
Antiviral activity against HCV genotype 1a in human Huh-7 replicon cells assessed as EC50 by replicon assay.
|
40054502 |
| Huh-7 | EC50 |
2 pM
|
Antiviral activity against HCV genotype 1b in human Huh-7 replicon cells assessed as EC50 by replicon assay.
Antiviral activity against HCV genotype 1b in human Huh-7 replicon cells assessed as EC50 by replicon assay.
|
40054502 |
| Huh-7 | EC50 |
4 pM
|
Antiviral activity against HCV genotype 2b in human Huh-7 replicon cells assessed as EC50 by replicon assay.
Antiviral activity against HCV genotype 2b in human Huh-7 replicon cells assessed as EC50 by replicon assay.
|
40054502 |
| Huh-7.5 | EC50 |
0.010 nM
|
Antiviral activity against transient HCV GT1a isolate NC004102 (H77) replicon in Huh7.5 cells assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient HCV GT1a isolate NC004102 (H77) replicon in Huh7.5 cells assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.003 nM
|
Antiviral activity against transient HCV GT1a isolate EU781816 replicon in Huh7.5 cells assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient HCV GT1a isolate EU781816 replicon in Huh7.5 cells assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.002 nM
|
Antiviral activity against transient HCV GT1a isolate AY956464 replicon in Huh7.5 cells assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient HCV GT1a isolate AY956464 replicon in Huh7.5 cells assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.005 nM
|
Antiviral activity against transient HCV GT1a isolate AY956463 replicon in Huh7.5 cells assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient HCV GT1a isolate AY956463 replicon in Huh7.5 cells assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.007 nM
|
Antiviral activity against transient HCV GT1b isolate AJ238799 (Con1) replicon in Huh7.5 cells assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient HCV GT1b isolate AJ238799 (Con1) replicon in Huh7.5 cells assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.006 nM
|
Antiviral activity against transient HCV GT1b isolate AB049087 replicon in Huh7.5 cells assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient HCV GT1b isolate AB049087 replicon in Huh7.5 cells assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.004 nM
|
Antiviral activity against transient HCV GT1b isolate EF407458 replicon in Huh7.5 cells assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient HCV GT1b isolate EF407458 replicon in Huh7.5 cells assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.014 nM
|
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with WT NS5A assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with WT NS5A assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.016 nM
|
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A M28A substitution assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A M28A substitution assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.015 nM
|
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Q30E substitution assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Q30E substitution assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.013 nM
|
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Q30H substitution assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Q30H substitution assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.019 nM
|
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Q30K substitution assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Q30K substitution assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.011 nM
|
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Q30L substitution assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Q30L substitution assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.012 nM
|
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Q30N substitution assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Q30N substitution assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.017 nM
|
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Q30R substitution assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Q30R substitution assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.018 nM
|
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A L31M substitution assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A L31M substitution assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.076 nM
|
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A L31V substitution assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A L31V substitution assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.026 nM
|
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A H58R substitution assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A H58R substitution assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.038 nM
|
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Y93H substitution assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Y93H substitution assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
| Huh-7.5 | EC50 |
0.090 nM
|
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Y93N substitution assessed by Gaussia luciferase after 72 hrs incubation.
Antiviral activity against transient full-length HCV GT1a H77 replicon in Huh7.5 cells with NS5A Y93N substitution assessed by Gaussia luciferase after 72 hrs incubation.
|
30150466 |
In Vitro
Ruzasvir is a highly potent HCV NS5A inhibitor, with EC50 values of 1-4 pM against the tested HCV genotypes in Huh-7 replicons and an EC50 of 5.0 pM against HCV GT1b in Huh-luc/neo-ET reporter replicon cells[5].
Ruzasvir inhibits HCV RNA replication of HCV GT1-GT7 in Huh7/Huh7.5 stable replicon cells, with EC50 of 0.0007-0.004 nM, and GT1a H77 maintains an EC50 of 0.010 nM in 40% normal serum[6].
Ruzasvir (0.01-20× EC90; 72 h) in combination with Grazoprevir or Uprifosbuvir analogs produces additive to synergistic inhibition of GT1a or GT3 replicon RNA, without antagonism or cytotoxicity[6].
Ruzasvir inhibits HCV replicon genotypes 1-6, with EC90 = 0.003 nM against GT1a (H77) and maintains EC90 = 0.067 nM against GT1a Y93H[7].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:GT1a and GT3 HCV replicon cells
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Concentration:0.01 to 20× EC90 for each compound
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Incubation Time:72 h
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Result:Combined with grazoprevir in GT1a replicon cells: run 1 log volume 0/−0.68, additive; run 2 4.03/0, minor synergy; run 3 2.42/0, minor synergy.
Combined with uprifosbuvir analogue in GT3 replicon cells: run 1 41.01/0, strong synergy; run 2 14.71/−0.37, strong synergy; run 3 23.83/0, strong synergy.
No appreciable cytotoxicity was observed in either GT1a or GT3 replicon cells.
Parmacokinetics
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 1613081-64-3
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Appearance Solid
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Molecular Weight 947.09
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Formula C49H55FN10O7S
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Color Light yellow to yellow
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SMILES
FC1=C2C3=CC4=CC(C5=CN=C([C@H](CCC6)N6C([C@H](C(C)C)NC(OC)=O)=O)N5)=CC=C4N3[C@H](C7=CN=C(C8CC8)S7)OC2=CC(C9=CN=C([C@H](CCC%10)N%10C([C@H](C(C)C)NC(OC)=O)=O)N9)=C1
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Synonyms
MK-8408
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (105.59 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
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Data Sheet (276 KB)
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SDS (396 KB)
- English - EN (396 KB)
- Français - FR (396 KB)
- Deutsch - DE (396 KB)
- Norwegian - NO (396 KB)
- Español - ES (396 KB)
- Swedish - SV (396 KB)
- Italian - IT (396 KB)
- Korean - KR (396 KB)
- Portuguese - PT (396 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.0559 mL | 5.2793 mL | 10.5587 mL | 26.3966 mL |
| 5 mM | 0.2112 mL | 1.0559 mL | 2.1117 mL | 5.2793 mL | |
| 10 mM | 0.1056 mL | 0.5279 mL | 1.0559 mL | 2.6397 mL | |
| 15 mM | 0.0704 mL | 0.3520 mL | 0.7039 mL | 1.7598 mL | |
| 20 mM | 0.0528 mL | 0.2640 mL | 0.5279 mL | 1.3198 mL | |
| 25 mM | 0.0422 mL | 0.2112 mL | 0.4223 mL | 1.0559 mL | |
| 30 mM | 0.0352 mL | 0.1760 mL | 0.3520 mL | 0.8799 mL | |
| 40 mM | 0.0264 mL | 0.1320 mL | 0.2640 mL | 0.6599 mL | |
| 50 mM | 0.0211 mL | 0.1056 mL | 0.2112 mL | 0.5279 mL | |
| 60 mM | 0.0176 mL | 0.0880 mL | 0.1760 mL | 0.4399 mL | |
| 80 mM | 0.0132 mL | 0.0660 mL | 0.1320 mL | 0.3300 mL | |
| 100 mM | 0.0106 mL | 0.0528 mL | 0.1056 mL | 0.2640 mL |