Physicochemical Properties
| Molecular Formula | C22H19CLO6 |
| Molecular Weight | 414.835665941238 |
| Exact Mass | 414.09 |
| CAS # | 2919019-72-8 |
| Related CAS # | trans-ccc_R08;2413192-49-9;cis-ccc_R08;2413192-48-8 |
| PubChem CID | 146443478 |
| Appearance | White to yellow solid powder |
| LogP | 3.7 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 29 |
| Complexity | 635 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | ClC1=CC=CC2C(C=C(C3C=CC(=CC=3)OCCOC3CC(C(=O)O)C3)OC=21)=O |
| InChi Key | JFCQXBCQZCBQSI-UHFFFAOYSA-N |
| 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) |
| Chemical Name | 3-[2-[4-(8-chloro-4-oxochromen-2-yl)phenoxy]ethoxy]cyclobutane-1-carboxylic acid |
| Synonyms | ccc_R08 |
| 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 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) |
Biological Activity
| Targets | cccDNA |
| 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]. |
| 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]. |
| 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 ). |
| 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. |
| References |
[1]. Discovery of a first-in-class orally available HBV cccDNA inhibitor. J Hepatol. 2022 Dec 29:S0168-8278(22)03466-3. [2]. Targeting Viral cccDNA for Cure of Chronic Hepatitis B. Curr Hepatol Rep. 2020 Sep;19(3):235-244. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~241.1 mM) |
| 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. 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. 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 | 2.4106 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 |