| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
|
||
| 500mg |
| Targets |
TMF targets the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor involved in xenobiotic metabolism, immune response, and cell proliferation. It acts as an antagonist (EC50 = 0.9 uM), competing with agonists such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for binding to AhR. It shows no short-term agonist activity and no species or promoter dependence.
|
|---|---|
| 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.
In vitro, 6,2',4'-Trimethoxyflavone (0.1-10 uM) inhibits AhR-mediated gene induction, suppressing the expression of CYP1A1, a canonical AhR target gene. It blocks the kynurenine (Kyn)-dependent modulation of CYP1A1. The compound modulates signaling pathways involved in cell proliferation, apoptosis, and immune responses, including effects on MAPK and NF-kappaB activity. |
| 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].
In vivo, 6,2',4'-Trimethoxyflavone has demonstrated anticancer activity in xenograft mouse models, reducing tumor volume. It shows anti-inflammatory effects in rodent models of inflammation, likely through AhR antagonism leading to reduced production of pro-inflammatory cytokines (IL-6, TNFalpha, IL-17). The compound also exhibits antioxidant properties in vivo. |
| Enzyme Assay |
For non-cellular AhR binding, recombinant human AhR protein is incubated with a fluorescently labeled AhR ligand (e.g., Texas Red-TCDD) or radiolabeled [3H]TCDD in the presence of varying concentrations of 6,2',4'-Trimethoxyflavone (0.001-100 uM). After equilibrium, binding is measured by fluorescence polarization (FP) or scintillation counting to determine IC50 and Ki for antagonism.
|
| 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 . For cell-based AhR inhibition, HepG2 or murine Hepa-1c1c7 cells are transiently transfected with a CYP1A1-luciferase reporter construct and treated with 6,2',4'-Trimethoxyflavone (0.01-10 uM) for 24-48 hours in the presence or absence of an AhR agonist (e.g., 1-10 nM TCDD or 10-100 uM kynurenine). Luciferase activity is measured, and IC50 is calculated for inhibition of agonist-induced reporter activity. CYP1A1 mRNA is quantified by qRT-PCR. |
| 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. For in vivo evaluation, male C57BL/6 mice are dosed with 6,2',4'-Trimethoxyflavone (10-50 mg/kg) via oral gavage or intraperitoneal injection 1-2 hours prior to TCDD (5 ug/kg, i.p.) or kynurenine (100 mg/kg, i.p.). After 4-24 hours, liver and small intestine are harvested. CYP1A1 mRNA and protein levels are quantified by qRT-PCR and Western blot. For xenograft models, athymic nude mice are implanted with cancer cells, and TMF (10-50 mg/kg) is administered daily for 2-4 weeks. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for 6,2',4'-Trimethoxyflavone are limited. As a flavonoid (MW 312.32, C18H16O5), it is expected to have moderate oral bioavailability and a short half-life (2-6 hours) due to rapid glucuronidation and sulfation. No formal PK studies are published.
|
| Toxicity/Toxicokinetics |
Toxicity data for 6,2',4'-Trimethoxyflavone are limited. Flavonoids generally have low acute toxicity. In vitro cytotoxicity assessments in multiple cell lines show no significant reduction in viability at concentrations up to 50 uM. No in vivo toxicity studies have been reported.
|
| References |
|
| Additional Infomation |
6,2',4'-Trimethoxyflavone is a research-grade AhR antagonist, not approved for human therapy. It is valuable for studying AhR-dependent processes in cancer, inflammation, and immune regulation. The compound has potential as a chemopreventive or therapeutic agent in AhR-driven diseases. No clinical trials are registered.
|
| 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)
|
| 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 |
*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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
