Danoprevir
Based on 20 publication(s) in Google Scholar
Danoprevir (ITMN-191) is an orally active NS3/4A protease inhibitor for hepatitis C virus (HCV) with an IC50 of 0.29 nM and is selective for NS3/4A over a panel of 53 proteases (IC50 higher than 10 μM). Danoprevir (ITMN-191) inhibits HCV genotypes 1a, 1b, 4, 5, and 6 (IC50s=0.2-0.4 nM) as well as 2b and 3a (IC50s=1.6, 3.5 nM). Danoprevir is also a SARS-CoV 3CLpro inhibitor with an IC50 of 0.05 μM.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 99.67%
- No. CAS: 850876-88-9
- Fòrmula: C35H46FN5O9S
- Peso molecular:731.83
-
Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Actividad biológica
-
Chemical Information
-
Solvente y solubilidad
- Protocolo
- Pureza y Documentación
- Referencias
-
Help & FAQs
Publications Citing Use of MedChemExpress (MCE) Danoprevir
More- Signal Transduct Target Ther. 2021 May 29;6(1):212. [Abstract]
- Cell Res. 2024 Jan;34(1):31-46. [Abstract]
- Nat Methods. 2018 Jul;15(7):519-522. [Abstract]
- Nat Commun. 2014 Oct 30:5:5352. [Abstract]
- Int J Radiat Oncol Biol Phys. 2016 Nov 15;96(4):867-876. [Abstract]
- Avicenna J Phytomed. 2021 Jul-Aug;11(4):353-366. [Abstract]
- Fungal Biol. 2021 May;125(5):378-388. [Abstract]
- Virology. 2014 May:456-457:300-9. [Abstract]
- Boston University. 2025.
- bioRxiv. 2025 Aug 31:2025.08.26.672367. [Abstract]
- Patent. US12065501.
- University of Colorado Denver. 2024.
- bioRxiv. 2023 Mar 20:2023.03.20.533499. [Abstract]
- bioRxiv. 2023 Feb 27:2023.02.27.530290. [Abstract]
- Patent. US20210238569A1.
- bioRxiv. 2020 Apr.
- Patent. US20190010245A1.
- Patent. US20180346589A1.
- Patent. US20170233708A1.
- Seoul National University. 2016 Aug.
Customer Validation & Images
-
WB
Actividad biológica
IC50: 0.29 nM (NS3/4A protease), 0.2-3.5 nM (HCV genotypes 1a, 1b, 2b, 3a, 4, 5, 6)[2]
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| Huh-7 | EC50 |
<0.25 nM
Compound: 49, Danoprevir, ITMN-191, R7227
|
Antiviral activity against Hepatitis C virus harboring wild type NS3/4A protease infected in human HuH7 cells assessed as inhibition of HCV subgenomic replicon replication after 72 hrs by ELISA
Antiviral activity against Hepatitis C virus harboring wild type NS3/4A protease infected in human HuH7 cells assessed as inhibition of HCV subgenomic replicon replication after 72 hrs by ELISA
|
[PMID: 23672640] |
| Huh-7 | EC50 |
0.011 μM
Compound: 5
|
Antiviral activity against HCV infected in human HuH7 cells by cell based replicon assay
Antiviral activity against HCV infected in human HuH7 cells by cell based replicon assay
|
[PMID: 27160057] |
| Huh-7 | EC50 |
0.25 nM
Compound: ITMN-191
|
Antiviral activity against HCV1b harboring Q80Q polymorphism in NS3 protease gene infected in human Huh7/Lunet cells assessed as inhibition of viral replication after 3 days by luciferase based transient-transfection assay
Antiviral activity against HCV1b harboring Q80Q polymorphism in NS3 protease gene infected in human Huh7/Lunet cells assessed as inhibition of viral replication after 3 days by luciferase based transient-transfection assay
|
[PMID: 20855726] |
| Huh-7 | EC50 |
0.5 nM
Compound: 49, Danoprevir, ITMN-191, R7227
|
Antiviral activity against Hepatitis C virus harboring NS3/4A protease A156T mutant gene infected in human HuH7 cells assessed as inhibition of HCV subgenomic replicon replication after 72 hrs by ELISA
Antiviral activity against Hepatitis C virus harboring NS3/4A protease A156T mutant gene infected in human HuH7 cells assessed as inhibition of HCV subgenomic replicon replication after 72 hrs by ELISA
|
[PMID: 23672640] |
| Huh-7 | EC50 |
0.6 nM
Compound: ITMN-191
|
Antiviral activity against HCV1b Con1 harboring NS3 protease gene infected in human Huh7/Lunet cells assessed as inhibition of viral replication after 3 days by luciferase based transient-transfection assay
Antiviral activity against HCV1b Con1 harboring NS3 protease gene infected in human Huh7/Lunet cells assessed as inhibition of viral replication after 3 days by luciferase based transient-transfection assay
|
[PMID: 20855726] |
| Huh-7 | EC50 |
0.62 nM
Compound: ITMN-191
|
Antiviral activity against HCV1b harboring Q80K polymorphism in NS3 protease gene infected in human Huh7/Lunet cells assessed as inhibition of viral replication after 3 days by luciferase based transient-transfection assay
Antiviral activity against HCV1b harboring Q80K polymorphism in NS3 protease gene infected in human Huh7/Lunet cells assessed as inhibition of viral replication after 3 days by luciferase based transient-transfection assay
|
[PMID: 20855726] |
| Huh-7 | EC50 |
1 nM
Compound: ITMN191
|
Antiviral activity against HCV 1a infected in human Huh-7 cells after 48hrs by luciferase assay
Antiviral activity against HCV 1a infected in human Huh-7 cells after 48hrs by luciferase assay
|
[PMID: 21067923] |
| Huh-7 | EC50 |
1.1 nM
Compound: ITMN191
|
Antiviral activity against HCV 1b infected in human Huh-7 cells after 48hrs by luciferase assay
Antiviral activity against HCV 1b infected in human Huh-7 cells after 48hrs by luciferase assay
|
[PMID: 21067923] |
| Huh-7 | EC50 |
1.6 nM
Compound: 49, Danoprevir, ITMN-191, R7227
|
Antiviral activity against Hepatitis C virus genotype 1b infected in human HuH7 cells assessed as decrease in replicon RNA level after 2 days by TaqMan Gold RT-PCR analysis
Antiviral activity against Hepatitis C virus genotype 1b infected in human HuH7 cells assessed as decrease in replicon RNA level after 2 days by TaqMan Gold RT-PCR analysis
|
[PMID: 23672640] |
| Huh-7 | EC50 |
2.1 nM
Compound: RG-7227, ITMN-191
|
Antiviral activity against HCV 1B infected in human Huh7 cells by firefly luciferase reporter gene assay
Antiviral activity against HCV 1B infected in human Huh7 cells by firefly luciferase reporter gene assay
|
[PMID: 20541424] |
| Huh-7 | EC50 |
2.4 nM
Compound: 49, Danoprevir, ITMN-191, R7227
|
Antiviral activity against Hepatitis C virus infected in human HuH7 cells assessed as inhibition of HCV subgenomic replicon replication after 72 hrs by ELISA
Antiviral activity against Hepatitis C virus infected in human HuH7 cells assessed as inhibition of HCV subgenomic replicon replication after 72 hrs by ELISA
|
[PMID: 23672640] |
| Huh-7 | EC50 |
20 nM
Compound: 49, Danoprevir, ITMN-191, R7227
|
Antiviral activity against Hepatitis C virus genotype 2 infected in human HuH7 cells assessed as decrease in replicon RNA level after 2 days by TaqMan Gold RT-PCR analysis
Antiviral activity against Hepatitis C virus genotype 2 infected in human HuH7 cells assessed as decrease in replicon RNA level after 2 days by TaqMan Gold RT-PCR analysis
|
[PMID: 23672640] |
| Huh-7 | EC50 |
20 nM
Compound: 49, Danoprevir, ITMN-191, R7227
|
Antiviral activity against Hepatitis C virus genotype 3 infected in human HuH7 cells assessed as decrease in replicon RNA level after 2 days by TaqMan Gold RT-PCR analysis
Antiviral activity against Hepatitis C virus genotype 3 infected in human HuH7 cells assessed as decrease in replicon RNA level after 2 days by TaqMan Gold RT-PCR analysis
|
[PMID: 23672640] |
| Huh-7 | IC50 |
0.24 nM
Compound: 49, Danoprevir, ITMN-191, R7227
|
Antiviral activity against Hepatitis C virus genotype 1a isolate Con1 harboring wild type NS3/4A protease infected in human HuH7 cells assessed as inhibition of HCV replicon replication by luciferase assay
Antiviral activity against Hepatitis C virus genotype 1a isolate Con1 harboring wild type NS3/4A protease infected in human HuH7 cells assessed as inhibition of HCV replicon replication by luciferase assay
|
[PMID: 23672640] |
| Huh-7 | IC50 |
5.7 nM
Compound: 49, Danoprevir, ITMN-191, R7227
|
Antiviral activity against Hepatitis C virus genotype 1a isolate Con1 harboring NS3/4A protease A156T mutant gene infected in human HuH7 cells assessed as inhibition of HCV replicon replication by luciferase assay
Antiviral activity against Hepatitis C virus genotype 1a isolate Con1 harboring NS3/4A protease A156T mutant gene infected in human HuH7 cells assessed as inhibition of HCV replicon replication by luciferase assay
|
[PMID: 23672640] |
In Huh7.5 cells transfected with chimeric recombinant virus, Danoprevir (ITMN-191) shows antiviral inhibition effects against HCV genotypes 1, 4 and 6 with IC50 of 2-3 nM, which are >100-fold lower than genotypes 2/3/5 (280-750 nM)[1].
Danoprevir (ITMN-191) inhibits the reference genotype 1 NS3/4A protease half-maximally, but a high dose of Danoprevir (ITMN-191) (10 μM) shows no appreciably inhibition in a panel of 79 proteases, ion channels, transporters, and cell surface receptors. Danoprevir (ITMN-191) remains bound to and inhibits NS3/4A for more than 5 hours after its initial association. Danoprevir (ITMN-191) (45 nM) eliminates a patient-derived HCV genotype 1b replicon from hepatocyte-derived Huh7 cells with an EC50 of 1.8 nM[2].
In HCV subgenomic replicon cell lines containing the individual mutations, V36M, R109K, and V170A substitutions confer little or no resistance to Danoprevir (ITMN-191), but the R155K substitution confers a high level (62-fold increase) of resistance to Danoprevir[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
-
No. CAS 850876-88-9
-
Appearance Solid
-
Peso molecular 731.83
-
Fòrmula C35H46FN5O9S
-
Color White to off-white
-
SMILES
O=S(NC([C@@]1(NC([C@]2([H])C[C@@H](OC(N3CC4=C(C3)C=CC=C4F)=O)CN2C5=O)=O)C[C@]1(/C=C/CCCCC[C@@H]5NC(OC(C)(C)C)=O)[H])=O)(C6CC6)=O
-
Synonyms
ITMN-191; R7227; RO5190591; RG7227
-
Envío
Room temperature in continental US; may vary elsewhere.
-
Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (20)
-
Journal Impact Factor
-
Most Recent
-
Signal Transduct Target Ther
Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease. [Abstract]2021 May 29;6(1):212. PMID: 34052830 -
Cell Res
Engineered poly(A)-surrogates for translational regulation and therapeutic biocomputation in mammalian cells. [Abstract]2024 Jan;34(1):31-46. PMID: 38172533 -
Nat Methods
2018 Jul;15(7):519-522. PMID: 29967495 -
Nat Commun
A system for the continuous directed evolution of proteases rapidly reveals drug-resistance mutations. [Abstract]2014 Oct 30:5:5352. PMID: 25355134 -
Int J Radiat Oncol Biol Phys
Targeting Phosphatidylinositol 4-Kinase IIIα for Radiosensitization: A Potential Model of Drug Repositioning Using an Anti-Hepatitis C Viral Agent. [Abstract]2016 Nov 15;96(4):867-876. PMID: 27788957 -
Avicenna J Phytomed
Inhibitory activity of limonoids from Khaya grandifoliola C.DC (Meliaceae) against hepatitis C virus infection in vitro. [Abstract]2021 Jul-Aug;11(4):353-366. PMID: 34290967 -
Fungal Biol
The serine peptidase inhibitor N-ρ-tosyl-l-phenylalanine chloromethyl ketone (TPCK) affects the cell biology of Candida haemulonii species complex. [Abstract]2021 May;125(5):378-388. PMID: 33910679 -
Virology
Human pegivirus (GB virus C) NS3 protease activity inhibits induction of the type I interferon response and is not inhibited by HCV NS3 protease inhibitors. [Abstract]2014 May:456-457:300-9. PMID: 24889249
Danoprevir purchased from MedChemExpress. Usage Cited in: Virology. 2014 May:456-457:300-9. [Abstract]
Jurkat cells are transfected with plasmids expressing (A) HCV NS3/4A or (B) HPgV NS3/4AB-HA. Telaprevir, Boceprevir, and Danoprevir are added at concentrations of 100 µM, 16.6 µM, 2.7 µM, or 0 µM in 0.1% DMSO. Lysates are harvested after 24 h and resolved by immunoblots probed with anti-HCV NS3 (A) or anti-HA (B). The position of HCV NS3/4A (~75kDa), HCV NS3 (~73kDa), NS3/4AB-HA, and NS4B-HA (~30kDa) are indicated. Molecular markers are on the right.
-
-
bioRxiv
Replating induces mTOR-dependent rescue of protein synthesis in Charcot-Marie-Tooth diseased neurons. [Abstract]2025 Aug 31:2025.08.26.672367. PMID: 40909707 -
-
-
bioRxiv
Orthogonal inducible control of Cas13 circuits enables programmable RNA regulation in mammalian cells. [Abstract]2023 Mar 20:2023.03.20.533499. PMID: 36993327 -
bioRxiv
Controlled protein activities with viral proteases, antiviral peptides, and antiviral drugs. [Abstract]2023 Feb 27:2023.02.27.530290. PMID: 36909459 -
-
-
-
-
-
Solvente y solubilidad
DMSO : ≥ 100 mg/mL (136.64 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (3.42 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocolo
The assay buffer contains 25 μM NS4A peptide, 50 mM Tris-HCl, pH 7.5, 15% (vol/vol) glycerol, 0.6 mM lauryldimethylamine N-oxide, 10 mM dithiothreitol, and 0.5 μM fluorescein/QXL520-labeled FRET substrate {Ac-DE-Dap(QXL520)-EE-Abu-ψ-[COO]-AS-Cys(5-FAMsp)-NH2}. K2040 enzyme (50 pM) is added to initiate the reaction. Reactions are set up in black 96-well plates, and fluorescence data is collected. Control reactions lacking inhibitors and enzyme are included. Initial rates are calculated from the linear phase of the reaction (up to 1 hour) and are used to obtain IC50. Recovery of activity from preformed Danoprevir-NS3/4A complex is assessed by preincubating 10 nM NS3/4A with a two-fold excess of Danoprevir in 1× assay buffer for 15 min, followed by a rapid 200-fold dilution of the preformed complex into assay buffer containing substrate. A control reaction with the same final conditions without preincubation of NS3/4A and Danoprevir is initiated by the addition of enzyme to an otherwise-complete reaction mixture. Additional control reactions lack either Danoprevir or NS3. The progress of the reactions is followed over 5 hours.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Pharmacokinetic properties are evaluated in rats and monkeys. Sprague-Dawley rats (three per time point) are administered a 30-mg/kg of body weight dose of ITMN-191 by oral gavage (a 6-mg/mL solution in water). Cynomolgus monkeys (two per time point) are administered a 30-mg/kg dose of ITMN-191 by oral gavage (a 3-mg/mL solution in water). For each species, terminal blood samples and the entire perfused liver are collected 1, 4, 8, 12, and 24 h after dose administration. Blood samples are collected in EDTA, processed for plasma by centrifugation at 5°C, and stored at −20°C until analysis is performed. Liver samples are snap-frozen and stored at −70°C until analysis is performed. Blank, standard, and unknown plasma samples and homogenized liver containing an internal standard (ITMN-191 analog) are treated with acidified acetonitrile and centrifuged to remove precipitated proteins. The density of liver tissue is taken into account to allow concentrations in both compartments to be expressed as weight per unit volume. The cleared supernatants are diluted 1:1 into high-performance liquid chromatography grade water and analyzed on a 4000 Q-trap liquid chromatography-tandem mass spectrometer fitted with the Turbo-Ionspray source operating in negative-ion mode. Analytes and internal standards are monitored using multiple-reaction-monitoring scans and calibrated with ABI Analyst software, version 1.4.2. The calibration standards ranges from 0.0169 ng/mL to 37.0 ng/mL and from 7.47 ng/mL to 5,440 ng/mL for the quantification of plasma samples and liver homogenates, respectively. Quadratic fitting with 1/x weighting is utilized where an R2 value of > 0.999 is achieved in both matrices.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Pureza y Documentación
-
Ficha de datos (290 KB)
-
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
-
Instrucciones de manejo (2659 KB)
Referencias
[1]. Imhof I, et al. Genotype differences in susceptibility and resistance development of hepatitis C virus to protease inhibitors telaprevir (VX-950) and danoprevir (ITMN-191).Hepatology. 2011 Apr;53(4):1090-9. [Content Brief]
[3]. Bartels DJ, et al. Natural prevalence of hepatitis C virus variants with decreased sensitivity to NS3.4A protease inhibitors in treatment-naive subjects. J Infect Dis. 2008 Sep 15;198(6):800-7. [Content Brief]
[4]. Qi Sun, et al. Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease. Signal Transduct Target Ther. 2021 May 29;6(1):212. [Content Brief]
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.3664 mL | 6.8322 mL | 13.6644 mL | 34.1609 mL |
| 5 mM | 0.2733 mL | 1.3664 mL | 2.7329 mL | 6.8322 mL | |
| 10 mM | 0.1366 mL | 0.6832 mL | 1.3664 mL | 3.4161 mL | |
| 15 mM | 0.0911 mL | 0.4555 mL | 0.9110 mL | 2.2774 mL | |
| 20 mM | 0.0683 mL | 0.3416 mL | 0.6832 mL | 1.7080 mL | |
| 25 mM | 0.0547 mL | 0.2733 mL | 0.5466 mL | 1.3664 mL | |
| 30 mM | 0.0455 mL | 0.2277 mL | 0.4555 mL | 1.1387 mL | |
| 40 mM | 0.0342 mL | 0.1708 mL | 0.3416 mL | 0.8540 mL | |
| 50 mM | 0.0273 mL | 0.1366 mL | 0.2733 mL | 0.6832 mL | |
| 60 mM | 0.0228 mL | 0.1139 mL | 0.2277 mL | 0.5693 mL | |
| 80 mM | 0.0171 mL | 0.0854 mL | 0.1708 mL | 0.4270 mL | |
| 100 mM | 0.0137 mL | 0.0683 mL | 0.1366 mL | 0.3416 mL |
Danoprevir Related Classifications
HY-10238 Related Classifications
Powered by Bioz