| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
cccDNA
ccc_R08 targets covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV). cccDNA is the viral persistence reservoir that serves as the template for all viral transcripts in HBV infection. By inhibiting cccDNA, ccc_R08 reduces extracellular levels of HBV DNA, HBsAg, and HBeAg. The compound is non-cytotoxic and orally active. It has also been shown to be effective against HCV. |
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| ln Vitro |
In HepDES19 cells, ccc_R08 (0.3, 1.0, 3.2, 10, 32 µM; 5 days) dramatically lowers the levels of cccDNA, protein-free RC-DNA, and double stranded linear DNA (DL-DNA)[1]. The amount of extracellular HBeAg from HepDES19 cells is dose-dependently reduced by ccc_R08 (0 -100 µM), with an IC50 of ~0.1 µM[1].
In vitro studies demonstrate that ccc_R08 is a non-cytotoxic cccDNA inhibitor. The compound reduces extracellular levels of HBV DNA, HBsAg, and HBeAg in a dose-dependent manner. It has been shown to be effective in the treatment of HCV. The compound's mechanism involves reducing cccDNA levels in infected cells. Further details on in vitro activity have not been extensively published. |
| ln Vivo |
In HBVcircle mice, ccc_R08 (20 mg/kg; po; twice daily for 2 weeks) removes cccDNA from the liver[1]. The serum level of pgRNA is significantly reduced by ccc_R08 (10, 15, 20, 30 mg/kg; po; twice daily for 2 weeks), and at different doses, there is a quantitative correlation between the reduction in pgRNA and that in liver cccDNA[1].
In vivo, ccc_R08 reduces cccDNA levels in the liver of HBV-infected mice. The compound is orally active. It reduces extracellular levels of HBV DNA, HBsAg, and HBeAg in a dose-dependent manner. ccc_R08 has been shown to be effective in the treatment of HCV. The compound is non-cytotoxic. These findings support its potential for treating HBV infections. |
| Enzyme Assay |
The cccDNA inhibitory activity of ccc_R08 can be assessed using HBV-infected cell lines or primary hepatocytes. In a typical assay, cells are treated with varying concentrations of ccc_R08. cccDNA levels are measured by quantitative PCR using cccDNA-specific primers. Extracellular HBV DNA, HBsAg, and HBeAg levels are measured by qPCR or ELISA. Cytotoxicity is assessed using MTT assays to confirm the compound's non-cytotoxic profile.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: HepDES19 cells Tested Concentrations: 0.3, 1.0, 3.2, 10, 32 µM Incubation Duration: 5 days Experimental Results: decreased the level of cccDNA, protein-free RC-DNA, and double stranded linear DNA (DL-DNA ). The cellular activity of ccc_R08 is assessed using HBV-infected cell lines. Cells are treated with varying concentrations of ccc_R08. cccDNA levels are measured by quantitative PCR using cccDNA-specific primers. Extracellular HBV DNA, HBsAg, and HBeAg levels are measured by qPCR or ELISA. Cytotoxicity is assessed using MTT assays to confirm the compound's non-cytotoxic profile. The compound's activity against HCV can be assessed using HCV replicon systems. |
| Animal Protocol |
Animal/Disease Models: HBVcircle mouse model [1].
Doses: 20 mg/kg Route of Administration: Oral administration; twice per day for 2 weeks Experimental Results: Led to the clearance of cccDNA from HBVcircle mouse livers. Animal/Disease Models: HBVcircle mouse model [1] . Doses: 10, 15, 20, 30 mg/kg Route of Administration: Oral administration; twice per day for 42 days Experimental Results: Led to a sustained reduction in the serum levels of pgRNA. ccc_R08 has been evaluated in HBV-infected mouse models. In these studies, the compound is administered orally. cccDNA levels in the liver are measured by quantitative PCR. Extracellular HBV DNA, HBsAg, and HBeAg levels are measured in serum. The compound reduces cccDNA levels in a dose-dependent manner. It has also been shown to be effective against HCV in appropriate models. |
| ADME/Pharmacokinetics |
ccc_R08 is orally active, indicating favorable oral bioavailability. The compound has a LogP of 3.7 and a tPSA of 82.1. It has a hydrogen bond donor count of 1 and a hydrogen bond acceptor count of 6. The compound appears as a white to yellow solid powder. Further studies would be needed to fully characterize its absorption, distribution, metabolism, and excretion properties.
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| Toxicity/Toxicokinetics |
ccc_R08 is non-cytotoxic. As a cccDNA inhibitor, it may have effects on viral persistence without affecting cell viability. Comprehensive toxicology studies would be required to evaluate its safety profile for potential therapeutic development. The compound is intended for research use only.
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| References | |
| Additional Infomation |
ccc_R08 (CAS# 2919019-72-8) is a non-cytotoxic and orally active cccDNA inhibitor that reduces cccDNA levels in the liver of HBV-infected mice. It reduces extracellular levels of HBV DNA, HBsAg, and HBeAg in a dose-dependent manner. ccc_R08 has been shown to be effective in the treatment of HCV. It has a LogP of 3.7 and a tPSA of 82.1. The compound is used in HBV research. It appears as a white to yellow solid powder.
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| Molecular Formula |
C22H19CLO6
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|---|---|
| Molecular Weight |
414.835665941238
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| Exact Mass |
414.09
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| CAS # |
2919019-72-8
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| Related CAS # |
trans-ccc_R08;2413192-49-9;cis-ccc_R08;2413192-48-8
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| PubChem CID |
146443478
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| Appearance |
White to yellow solid powder
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
29
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| Complexity |
635
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=CC=CC2C(C=C(C3C=CC(=CC=3)OCCOC3CC(C(=O)O)C3)OC=21)=O
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| InChi Key |
JFCQXBCQZCBQSI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H19ClO6/c23-18-3-1-2-17-19(24)12-20(29-21(17)18)13-4-6-15(7-5-13)27-8-9-28-16-10-14(11-16)22(25)26/h1-7,12,14,16H,8-11H2,(H,25,26)
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| Chemical Name |
3-[2-[4-(8-chloro-4-oxochromen-2-yl)phenoxy]ethoxy]cyclobutane-1-carboxylic acid
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| Synonyms |
ccc_R08
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : ~100 mg/mL (~241.1 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.03 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 (6.03 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (6.03 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4106 mL | 12.0528 mL | 24.1057 mL | |
| 5 mM | 0.4821 mL | 2.4106 mL | 4.8211 mL | |
| 10 mM | 0.2411 mL | 1.2053 mL | 2.4106 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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