Fraxinellone is a naturally occurring anti-inflammatory agent isolated from the root bark of the Rutaceae plant, Dictamnus dasycarpus. Fraxinellone acts a PD-L1 inhibitor and inhibitor of HIF-1α protein synthesis without affecting HIF-1α protein degradation. Fraxinellone was able to inhibit LPS-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production, and to reduce the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels in a dose-dependent manner.
Physicochemical Properties
| Molecular Formula | C14H16O3 |
| Molecular Weight | 232.2750 |
| Exact Mass | 232.109 |
| CAS # | 28808-62-0 |
| PubChem CID | 124039 |
| Appearance | White to off-white solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 372.9±30.0 °C at 760 mmHg |
| Melting Point | 116ºC |
| Flash Point | 179.3±24.6 °C |
| Vapour Pressure | 0.0±0.8 mmHg at 25°C |
| Index of Refraction | 1.552 |
| LogP | 2.85 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 17 |
| Complexity | 385 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | CC1=C2C(=O)O[C@H]([C@@]2(CCC1)C)C3=COC=C3 |
| InChi Key | XYYAFLHHHZVPRN-GXTWGEPZSA-N |
| InChi Code | InChI=1S/C14H16O3/c1-9-4-3-6-14(2)11(9)13(15)17-12(14)10-5-7-16-8-10/h5,7-8,12H,3-4,6H2,1-2H3/t12-,14+/m0/s1 |
| Chemical Name | (3R,3aR)-3-(furan-3-yl)-3a,7-dimethyl-3,4,5,6-tetrahydro-2-benzofuran-1-one |
| 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) |
Biological Activity
| ln Vitro | In A549 cells, fraxinellone (0-100 μM; 12 hours) lowers the proportion of PD-L1-positive cells from 20.4% to 11.4% [1]. |
| ln Vivo | Oral gavage of fraxinellone (30 and 100 mg/kg; every three days; 30 days) effectively reduced the amount of HIF-1α, pTyr705 STAT3, PD-L1, and VEGF-stained animals and suppressed tumor growth [1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: A549 cells Tested Concentrations: 0 μM, 10 μM, 30 μM, 100 μM Incubation Duration: 12 hrs (hours) Experimental Results: Inhibited the percent of PD-L1 positive cells. |
| Animal Protocol |
Animal/Disease Models: BALB/c nude mice[1] Doses: 30 and 100 mg/kg Route of Administration: po (oral gavage); 30 and 100 mg/kg; every three days; 30 days Experimental Results: Dramatically suppressed tumor growth. |
| References |
[1]. Fraxinellone has anticancer activity in vivo by inhibiting programmed cell death-ligand 1 expression by reducing hypoxia-inducible factor-1α and STAT3. Pharmacol Res. 2018 Sep;135:166-180. |
| Additional Infomation |
Fraxinellone is a member of 2-benzofurans. Fraxinellone has been reported in Raulinoa echinata, Fagaropsis glabra, and other organisms with data available. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~430.51 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.76 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 (10.76 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 | 4.3051 mL | 21.5257 mL | 43.0515 mL | |
| 5 mM | 0.8610 mL | 4.3051 mL | 8.6103 mL | |
| 10 mM | 0.4305 mL | 2.1526 mL | 4.3051 mL |