| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg | |||
| Other Sizes |
| Targets |
The primary target of Anguizole is NS4B (nonstructural protein 4B), a viral protein found in hepatitis C virus that is a key regulator in HCV replication complex formation. NS4B plays a pivotal role in HCV replication by inducing specific membrane rearrangement and designating the membranous web. NS4B-AH2, comprising amino acids 42 to 66, is identified as a major regulator for NS4B oligomerization. Anguizole targets the second amphipathic helix of NS4B (NS4B-AH2). When tested with HCV virus, Anguizole treatment significantly disrupts NS4B-AH2-mediated biological functions, inhibiting HCV replication. The compound also disrupts NS4B's interaction with NS5A, another viral protein essential for HCV replication.
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| ln Vitro |
In vitro, Anguizole demonstrates potent inhibition of HCV replication. The compound has an IC₅₀ value of 310 nM for NS4B inhibition. In Huh7.5 cells transfected with a plasmid expressing NS4B fused in frame with GFP, 5 µM Anguizole treatment for 48 hours altered the distribution of NS4B, inhibiting the HCV life cycle. Anguizole treatment significantly disrupts NS4B-AH2-mediated biological functions. The compound also disrupts NS4B's dimerization and multimerization as well as its interaction with NS5A, further inhibiting viral genome replication. These in vitro studies demonstrate the compound's potential as an HCV antiviral agent.
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| ln Vivo |
In vivo, Anguizole's activity has been demonstrated in HCV replication models. The compound's ability to inhibit HCV replication makes it a promising candidate for the treatment of chronic hepatitis C infection. Anguizole targets a viral protein (NS4B) that is essential for HCV replication, potentially overcoming resistance to direct-acting antivirals that target other viral proteins. The compound's mechanism of action involves disrupting NS4B-AH2-mediated functions and NS4B-NS5A interactions. Further in vivo studies are needed to fully characterize its efficacy and safety in animal models of HCV infection.
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| Enzyme Assay |
In vitro enzyme/receptor binding studies for Anguizole focus on its interaction with NS4B. Binding affinity to NS4B can be assessed using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). The compound's ability to disrupt NS4B oligomerization can be evaluated using co-immunoprecipitation or crosslinking assays. NS4B-NS5A interaction assays can be performed using co-immunoprecipitation or FRET-based assays. IC₅₀ values for NS4B inhibition are determined from dose-response curves in cell-based replication assays. These methods are for research purposes only.
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| Cell Assay |
In vitro cell-based assays for Anguizole evaluate its anti-HCV activity. Huh7.5 cells or other HCV-permissive cell lines are transfected with HCV replicons or infected with HCV virus. Cells are treated with Anguizole at various concentrations (typically 0.1-10 µM) for 24-72 hours. HCV RNA levels are measured by qRT-PCR, and HCV protein expression is assessed by Western blot or immunofluorescence. NS4B subcellular distribution is examined by fluorescence microscopy. Cell viability is assessed using MTT or CCK-8 assays to ensure that observed antiviral effects are not due to cytotoxicity. Standard cell culture conditions are used with appropriate media and supplementation.
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| Animal Protocol |
In vivo animal studies for Anguizole would typically involve mouse models of HCV infection. However, HCV does not readily infect mice, so humanized mouse models (e.g., immunodeficient mice engrafted with human hepatocytes) are used for HCV replication studies. Anguizole is administered via oral or intraperitoneal routes at various doses. HCV RNA levels in serum and liver are measured by qRT-PCR. Liver histology is performed to assess the extent of infection and inflammation. Pharmacodynamic studies evaluate NS4B target engagement and disruption of NS4B functions. All procedures must comply with institutional animal care guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Anguizole are not fully characterized in publicly available literature. The compound has a molecular weight of 408.81 g/mol and is soluble in DMSO. Storage: store at -20°C. The compound's half-life, Cmax, AUC, and clearance would need to be determined in preclinical pharmacokinetic studies. The compound is for research use only and is not approved for clinical use. Further studies are needed to fully characterize its pharmacokinetic properties.
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| Toxicity/Toxicokinetics |
The toxicity profile of Anguizole is not fully characterized in publicly available literature. The compound is classified for research use only and not for human consumption. Standard safety precautions for handling chemical compounds apply, including the use of personal protective equipment and working in a chemical fume hood. Preclinical toxicology studies would be required for clinical development. The compound should be handled with care due to its biological activity.
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| References | |
| Additional Infomation |
Additional information: Anguizole has the CAS number 442666-98-0 and the molecular formula C₁₇H₁₁ClF₂N₄O₂S. The compound is a selective NS4B inhibitor with an IC₅₀ value of 310 nM. Anguizole targets the second amphipathic helix of NS4B (NS4B-AH2) and disrupts NS4B-mediated biological functions. The compound alters NS4B's subcellular distribution and inhibits HCV replication. Anguizole also disrupts NS4B's dimerization/multimerization and its interaction with NS5A. The compound is soluble in DMSO and should be stored at -20°C. This product is for research use only and is not approved for clinical or therapeutic applications.
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| Molecular Formula |
C17H11CLF2N4O2S
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|---|---|
| Molecular Weight |
408.809647798538
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| Exact Mass |
408.026
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| Elemental Analysis |
C, 49.95; H, 2.71; Cl, 8.67; F, 9.29; N, 13.71; O, 7.83; S, 7.84
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| CAS # |
442666-98-0
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| PubChem CID |
1046082
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.843
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
561
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC(C1=CC(C2=CC=CO2)=NC2=CC(C(NCC3=CC=CS3)=O)=NN21)(F)F
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| InChi Key |
GBNREAYNZPJROB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H11ClF2N4O2S/c18-17(19,20)14-7-11(13-4-1-5-26-13)22-15-8-12(23-24(14)15)16(25)21-9-10-3-2-6-27-10/h1-8H,9H2,(H,21,25)
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| Chemical Name |
7-[chloro(difluoro)methyl]-5-(furan-2-yl)-N-(thiophen-2-ylmethyl)pyrazolo[1,5-a]pyrimidine-2-carboxamide
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| Synonyms |
Anguizole; 442666-98-0; DTXSID30359937; RefChem:319572; DTXCID50310989;
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~122.31 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.12 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4461 mL | 12.2306 mL | 24.4612 mL | |
| 5 mM | 0.4892 mL | 2.4461 mL | 4.8922 mL | |
| 10 mM | 0.2446 mL | 1.2231 mL | 2.4461 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.
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