| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
| Targets |
HCV NS3 protease[2]
ITMN 4077 targets the hepatitis C virus (HCV) NS3/4A serine protease. The NS3/4A protease is a validated drug target essential for the processing of the viral polyprotein and subsequent viral replication. By inhibiting this protease, ITMN 4077 disrupts the viral life cycle. The compound is a macrocyclic inhibitor that specifically suppresses HCV NS3 protease activity. |
|---|---|
| ln Vitro |
ITMN 4077 demonstrates potent in vitro activity against the Hepatitis C Virus (HCV) NS3 protease with an EC50 value of 2131 nM. It is applied to inhibit viral genome synthesis, providing mechanistic insight into replication suppression. ITMN 4077 has shown antiviral activity against HCV in infected human HuH7 cells, evaluated by inhibition of HCV subgenomic replicon replication with an EC50 of 2.131 μM.
|
| ln Vivo |
ITMN 4077 has been evaluated in preclinical studies for its antiviral efficacy in vivo. As an orally bioavailable compound, it is suitable for oral administration in animal models. Preclinical studies have shown promise in treating viral infections by suppressing HCV replication. However, detailed in vivo efficacy data and comprehensive animal model studies are primarily available in the primary literature and clinical trial reports.
|
| Enzyme Assay |
For HCV NS3 protease inhibition assays, purified NS3/4A protease is incubated with a fluorogenic peptide substrate and ITMN 4077 at various concentrations. Protease activity is measured by fluorescence increase upon cleavage of the substrate. EC50 values are calculated from dose-response curves. Inhibition and binding kinetics studies have been conducted to characterize the compound's tight binding and slow dissociative behavior. Selectivity profiling is conducted by screening against related proteases.
|
| Cell Assay |
For antiviral activity evaluation, human HuH7 cells are cultured in appropriate media and infected with HCV or transfected with HCV subgenomic replicon. Cells are treated with ITMN 4077 at various concentrations for 24-72 hours. Viral replication is assessed by measuring HCV RNA levels or reporter gene expression. EC50 values are determined from dose-response curves. Cytotoxicity is assessed in parallel using standard cell viability assays to determine the selectivity index.
|
| Animal Protocol |
For in vivo efficacy studies, appropriate animal models of HCV infection would be used. ITMN 4077 would be administered orally at various doses. Viral load in plasma and liver tissues would be measured by qRT-PCR. Pharmacokinetic studies would determine compound exposure in plasma and target tissues. Efficacy would be evaluated by measuring viral titer reduction and histopathological analysis of liver tissues. However, detailed in vivo protocols for ITMN 4077 are primarily documented in the primary literature.
|
| ADME/Pharmacokinetics |
ITMN 4077 is an orally bioavailable compound with favorable pharmacokinetic properties. It has a molecular formula of C26H40N4O8S and a molecular weight of 568.68. The compound is a solid and should be stored as powder at -20°C for up to 3 years, or in solvent at -80°C for 6 months or -20°C for 1 month. It is soluble in DMSO and other organic solvents. Comprehensive PK parameters such as half-life, Cmax, and AUC have been characterized in preclinical studies.
|
| Toxicity/Toxicokinetics |
ITMN 4077 has been investigated in preclinical studies for antiviral applications, with promising results in suppressing HCV replication. The compound has a purity of 99.65%. It is a research compound intended for laboratory use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling this compound.
|
| References |
|
| Additional Infomation |
ITMN 4077 (danoprevir) is a potent, orally bioavailable, macrocyclic peptidomimetic inhibitor of the HCV NS3/4A serine protease. It suppresses HCV NS3 protease activity with an EC50 of 2131 nM. The compound has been investigated for antiviral applications and was in preclinical development for treating Hepatitis C infection. It is for research use only and has not been approved for clinical applications. Storage at -20°C as powder or in solvent is recommended.
|
| Molecular Formula |
C26H40N4O8S
|
|---|---|
| Molecular Weight |
568.6828
|
| Exact Mass |
568.256
|
| CAS # |
790305-05-4
|
| PubChem CID |
58798563
|
| Appearance |
White to off-white solid powder
|
| LogP |
1.6
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
39
|
| Complexity |
1120
|
| Defined Atom Stereocenter Count |
5
|
| SMILES |
S(C1([H])C([H])([H])C1([H])[H])(N([H])C([C@@]12C([H])([H])[C@@]1([H])C([H])=C([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[C@@]([H])(C(N1C([H])([H])[C@@]([H])(C([H])([H])[C@]1([H])C(N2[H])=O)O[H])=O)N([H])C(=O)OC(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])=O)(=O)=O
|
| InChi Key |
MXGKXZHTCMUVEE-JXUUZEIMSA-N
|
| InChi Code |
InChI=1S/C26H40N4O8S/c1-25(2,3)38-24(35)27-19-10-8-6-4-5-7-9-16-14-26(16,23(34)29-39(36,37)18-11-12-18)28-21(32)20-13-17(31)15-30(20)22(19)33/h7,9,16-20,31H,4-6,8,10-15H2,1-3H3,(H,27,35)(H,28,32)(H,29,34)/b9-7-/t16-,17-,19+,20+,26-/m1/s1
|
| Chemical Name |
tert-butyl N-[(1S,4R,6S,7Z,14S,18R)-4-(cyclopropylsulfonylcarbamoyl)-18-hydroxy-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-en-14-yl]carbamate
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (175.85 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.40 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.40 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.40 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7585 mL | 8.7923 mL | 17.5846 mL | |
| 5 mM | 0.3517 mL | 1.7585 mL | 3.5169 mL | |
| 10 mM | 0.1758 mL | 0.8792 mL | 1.7585 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
