Physicochemical Properties
| Molecular Formula | C18H16O5 |
| Molecular Weight | 312.317 |
| Exact Mass | 312.099 |
| CAS # | 720675-74-1 |
| PubChem CID | 688802 |
| Appearance | Yellow to orange solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 495.2±45.0 °C at 760 mmHg |
| Flash Point | 220.3±28.8 °C |
| Vapour Pressure | 0.0±1.3 mmHg at 25°C |
| Index of Refraction | 1.585 |
| LogP | 3.54 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 23 |
| Complexity | 460 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | WUWFDVDASNSUKP-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C18H16O5/c1-20-11-5-7-16-14(8-11)15(19)10-18(23-16)13-6-4-12(21-2)9-17(13)22-3/h4-10H,1-3H3 |
| Chemical Name | 2-(2,4-dimethoxyphenyl)-6-methoxychromen-4-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 | 6,2',4'-Trimethoxyflavone (TMF), as an AHR ligand, possesses antagonist qualities and is able to outcompete agonists like benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. This effectively prevents AHR-mediated transactivation of endogenous targets (like CYP1A1) and heterologous reporters, irrespective of kind of cell. TMF also works very well because it is not a partial agonist, unlike other known antagonists like α-naphthoflavone, which is a mild partial agonist. In AHR antagonistic interactions, TMF likewise exhibits no promoter or species dependence [1]. IC50 of 2.38 μM was observed for 6,2',4'-Trimethoxyflavone (0-100 μM; 72 hours) on TNF-⍺ production in THP-1 cells. The generation of TNF-α in B16-F10 cells is inhibited by 6,2',4'-trimethoxyflavone, with an IC50 of 1.32 μM. |
| ln Vivo | Compared with respective controls, WT mice treated with 6,2',4'-trimethoxyflavone (5 mg/kg/day; i.p.) demonstrated substantial decreases in infarct volume, sensorimotor and non-spatial skills. Memory function is improved[3]. |
| Cell Assay |
Cell viability assay [2] Cell Types: THP-1 cells, B16-F10 cells Tested Concentrations: 0-100 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibitory activity on TNF-⍺ production in THP-1 cells and B16-F10 cells . |
| Animal Protocol |
Animal/Disease Models: Male C57BL/6 wild-type (WT) mice, AHRcKO mice [3] Doses: 5 mg/kg/day Route of Administration: intraperitoneal (ip) injection Experimental Results: Both TMF-treated mice and AHRcKO mice can reduce acute cerebral infarction Infarction and dysfunction. |
| References |
[1]. Antagonism of aryl hydrocarbon receptor signaling by 6,2',4'-trimethoxyflavone [published correction appears in J Pharmacol Exp Ther. 2018 Nov;367(2):291]. J Pharmacol Exp Ther. 2010;332(1):135-144. [2]. Flavonoids of Tripodanthus acutifolius inhibit TNF-α production in LPS-activated THP-1 and B16-F10 cells. J Ethnopharmacol. 2019;242:112036. [3]. Aryl hydrocarbon receptor modulates stroke-induced astrogliosis and neurogenesis in the adult mouse brain. J Neuroinflammation. 2019;16(1):187. Published 2019 Oct 12. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~5 mg/mL (~16.01 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.5 mg/mL (1.60 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 5.0 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: ≥ 0.5 mg/mL (1.60 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 5.0 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2018 mL | 16.0092 mL | 32.0184 mL | |
| 5 mM | 0.6404 mL | 3.2018 mL | 6.4037 mL | |
| 10 mM | 0.3202 mL | 1.6009 mL | 3.2018 mL |