Danoprevir (ITMN-191)

Catalog No.S1183

Danoprevir(ITMN-191) is a peptidomimetic inhibitor of the NS3/4A protease of hepatitis C virus (HCV) with IC50 of 0.2-3.5 nM, inhibition effect for HCV genotypes 1A/1B/4/5/6 is ~10-fold higher than 2B/3A. Phase 2.

Price Stock Quantity  
USD 600 In stock
USD 120 In stock
USD 210 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

Danoprevir (ITMN-191) Chemical Structure

Danoprevir (ITMN-191) Chemical Structure
Molecular Weight: 731.83

Validation & Quality Control

3 customer reviews :

Quality Control & MSDS

Related Compound Libraries

Danoprevir (ITMN-191) is available in the following compound libraries:

Product Information

  • Compare HCV Protease Inhibitors
    Compare HCV Protease Products
  • Research Area
  • Danoprevir (ITMN-191) Mechanism

Product Description

Biological Activity

Description Danoprevir(ITMN-191) is a peptidomimetic inhibitor of the NS3/4A protease of hepatitis C virus (HCV) with IC50 of 0.2-3.5 nM, inhibition effect for HCV genotypes 1A/1B/4/5/6 is ~10-fold higher than 2B/3A. Phase 2.
Targets HCV NS3/4A protease [1]
IC50 0.2 nM-3.5 nM
In vitro Danoprevir (0.29 nM) inhibits the reference genotype 1 NS3/4A protease half-maximally, but a high dose of Danoprevir (10 μM) shows no appreciably inhibition in a panel of 79 proteases, ion channels, transporters, and cell surface receptors. Danoprevir remains bound to and inhibits NS3/4A for more than 5 hours after its initial association. Danoprevir (45 nM) eliminates a patient-derived HCV genotype 1b replicon from hepatocyte-derived Huh7 cells with an EC50 of 1.8 nM. [1] In HCV subgenomic replicon cell lines containing the individual mutations, V36M, R109K, and V170A substitutions confer little or no resistance to Danoprevir, but the R155K substitution confers a high level (62-fold increase) of resistance to Danoprevir. [2] In Huh7.5 cells transfected with chimeric recombinant virus, Danoprevir 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). [3]
In vivo Danoprevir (30 mg/kg) administered to rats or monkeys shows that its concentrations in liver 12 hours after dosing exceed the Danoprevir concentration required to eliminate replicon RNA from cells. [1]
Features A peptidomimetic inhibitor of the NS3/4A protease of hepatitis C virus (HCV).

Protocol(Only for Reference)

Kinase Assay: [1]

Continuous fluorescent resonance energy transfer (FRET) assay 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.

Cell Assay: [1]

Cell lines Huh7 cells harboring HCV replicon
Concentrations 5 pM - 100 nM
Incubation Time 48 hours
Method Serially diluted Danoprevir is added to Huh7 cells harboring the K2040 replicon 1 day after cell plating. For antiviral assays, after a 48-hour incubation, intracellular RNA is extracted, and the level of HCV replicon RNA is quantified by reverse transcription (RT)-PCR assay with the primers (5'-CACTCCCCTGTGAGGAACTACTG-3' and 5'-AGGCTGCACGACACTCATACT-3') and a probe (5'-6-FAM-CTTCACGCAGAAAGCGTCTAGCCATGG-MGBNFQ-3' using an ABI Prism 7900 sequence detection system. Here, FAM is 6-carboxyfluorescin and MGBNFQ is a molecular-groove binding non-fluorescence quencher specific to the HCV 5' untranslated region. Single-tube reactions are performed using the TaqMan Gold RT-PCR kit. Triplicate reactions for the RNA standards and samples are performed in 50 μL with 5 μL intracellular RNA (50 ng). RT is carried out at 48 °C for 30 min followed by 10 min at 95 °C. The PCR is run as follows: 15 seconds at 95 °C and 1 min at 60 °C for 40 cycles. Each RNA concentration is determined in triplicate. The absolute concentration of replicon RNA is calculated based on its signal relative to that of a standard curve generated by known concentrations of an in vitro-transcribed RNA corresponding to a genotype 1b 5' untranslated region. Replicon levels in the presence of Danoprevir are fitted to a four-parameter logistic function to obtain EC50.

Animal Study: [1]

Animal Models Sprague-Dawley rats, Cynomolgus monkeys
Formulation Dissolved in water. 6 mg/mL for rats and 3 mg/mL for monkeys
Dosages 30 mg/kg
Administration Oral gavage

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)
Body Surface Area (m2)0.0070.0250.
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)


[1] Seiwert SD, et al. Antimicrob Agents Chemother, 2008, 52(12), 4432-4441.

[2] Bartels DJ, et al. J Infect Dis, 2008, 198(6), 800-807.

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

NCT Number Recruitment Conditions Sponsor
Start Date Phases
NCT01749150 Completed Hepatitis C, Chronic Hoffmann-La Roche April 2013 Phase 2
NCT01714154 Completed Healthy Volunteer Hoffmann-La Roche November 2012 Phase 1
NCT01654211 Completed Healthy Volunteer Hoffmann-La Roche July 2012 Phase 1
NCT01579019 Withdrawn Hepatitis C, Chronic Hoffmann-La Roche July 2012 Phase 2
NCT01592318 Completed Healthy Volunteer Hoffmann-La Roche May 2012 Phase 1

view more

Chemical Information

Download Danoprevir (ITMN-191) SDF
Molecular Weight (MW) 731.83


CAS No. 850876-88-9
Storage 3 years -20℃powder
2 years -80℃in solvent
Synonyms RG7227
Solubility (25°C) * In vitro DMSO 144 mg/mL (196.76 mM)
Ethanol 144 mg/mL (196.76 mM)
Water <1 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name 2H-Isoindole-2-carboxylic acid, 4-fluoro-1,3-dihydro-, (2R,6S,13aS,14aR,16aS)-14a-[[(cyclopropylsulfonyl)amino]carbonyl]-6-[[(1,1-dimethylethoxy)carbonyl]amino]-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydro-5,16-dioxocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-2-yl ester

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related HCV Protease Products

  • Ledipasvir (GS5885)

    Ledipasvir (GS5885) is a HCV NS5A polymerase inhibitor, used for the treatment of hepatitis C virus infection.

  • Calpeptin

    Calpeptin is a potent, cell-permeable calpain inhibitor with ID50 of 52 nM, 34 nM, 138 nM, and 40 nM for Calpain I (porcine erythrocytes), Calpain II (porcine kidney), Papainb, and Calpain I (human platelets), respectively.

  • Marimastat(BB-2516)

    Marimastat (BB-2516) is a broad spectrum matrix metalloprotease (MMP) inhibitor for MMP-9, MMP-1, MMP-2, MMP-14 and MMP-7 with IC50 of 3 nM, 5 nM, 6 nM, 9 nM and 13 nM, respectively. Phase 3.

  • Daclatasvir (BMS-790052)

    Daclatasvir (BMS-790052) is a highly selective inhibitor of HCV NS5A with EC50 of 9-50 pM, for a broad range of HCV replicon genotypes and the JFH-1 genotype 2a infectious virus in cell culture. Phase 3.

    Features:First-in-class, highly selective inhibitor of hepatitis C virus (HCV) NS5A with picomolar EC50 values.

  • VX-222 (VCH-222, Lomibuvir)

    VX-222 (VCH-222) is a novel, potent and selective inhibitor of HCV polymerase with IC50 of 0.94-1.2 μM, 15.3-fold less effective for mutant M423T, and 108-fold less effective for mutant I482L. Phase 2.

    Features:A novel, potent and selective inhibitor of non-nucleoside polymerase, specifically the HCV RNA-dependent RNA polymerase.

  • Telaprevir (VX-950)

    Telaprevir (VX-950) is an HCV NS3-4A serine protease inhibitor with IC50 of 0.35 μM.

    Features:Telaprevir is a covalent, reversible inhibitor of the NS3-4A protease (unlike BILN 2061which is a noncovalent inhibitor), with a slow-binding and slow-dissociation mechanism.

  • MG-132

    MG-132 is an inhibitor of proteasome with IC50 of 100 nM in a cell-free assay, and also inhibits calpain with IC50 of 1.2 μM.

  • Bortezomib (PS-341)

    Bortezomib (PS-341) is a potent 20S proteasome inhibitor with Ki of 0.6 nM in a cell-free assay.

  • Carfilzomib (PR-171)

    Carfilzomib (PR-171) is an irreversible proteasome inhibitor with IC50 of <5 nM in ANBL-6 cells, displayed preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, but little or no effect on the PGPH and T-L activities.

  • Ixazomib (MLN2238)

    MLN2238 inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50 and Ki of 3.4 nM and 0.93 nM in cell-free assays, respectively, also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites, with IC50 of 31 and 3500 nM. Phase 3.

    Features:A first-in-class proteasome inhibitor that has improved pharmacokinetics (PK), pharmacodynamics(PD), and antitumor activity in preclinical studies.

Recently Viewed Items

Tags: buy Danoprevir (ITMN-191) | Danoprevir (ITMN-191) supplier | purchase Danoprevir (ITMN-191) | Danoprevir (ITMN-191) cost | Danoprevir (ITMN-191) manufacturer | order Danoprevir (ITMN-191) | Danoprevir (ITMN-191) distributor
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us