| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Breast cancer resistance protein (BCRP, named Bcrp1 in rodents) – an important efflux transporter involved in the elimination of the sulfated metabolite of Acacetin-7-Glucoside in vivo. [3]
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| ln Vitro |
Tilianin (10 μM, 20 μM) inhibits the release of pro-inflammatory cytokines in RAW264.7 macrophages stimulated by LPS (1 μg/mL) [2].
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| ln Vivo |
Improved treatment for LPS-induced acute lung damage (ALI) may involve the intraperitoneal injection of tirinalin (10 mg/kg) [2]. In mice, tiliin exhibits Tmax=10.8 min, Cmax=176.9 nmol/L, and AUC0-∞= 17.4 min*μmol/L[3].
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| Enzyme Assay |
For enzymatic synthesis of acacetin-7-glucuronide (Aca-7-G), acacetin (20 μM) was incubated with rat liver microsomes (0.25 mg/mL), MgCl₂ (0.88 mM), saccharolactone (4.4 mM), alamethicin (0.022 mg/mL), and uridine diphosphate glucuronic acid (UDPGA, 3.5 mM) in 50 mM potassium phosphate buffer (pH 7.4) at 37°C for 4 hours.
For enzymatic synthesis of acacetin-7-sulfate (Aca-7-S), acacetin (20 μM) was incubated with rat liver S9 fractions (4 mg/mL), MgCl₂ (40 mM), and 3'-Phosphoadenosine-5'-phosphosulfate (PAPS, 2 mM) in 50 mM potassium phosphate buffer (pH 7.4) at 37°C for 4 hours. To determine conversion factors (K values) of Aca-7-G and Aca-7-S, hydrolysis studies were performed. The K value was determined by comparing (a) the peak area change in acacetin after the metabolite was hydrolyzed by β-glucuronidases and/or sulfatases with (b) the corresponding peak area change in the metabolite. The K value was 1.2 for Aca-7-G and 1.7 for Aca-7-S. [3] |
| Animal Protocol |
Animal/Disease Models: C57BL/6 mice [2]
Doses: 10 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results: Macrophage infiltration and histopathological changes were attenuated, and inflammation was improved. Animal/Disease Models: Male FVB mice (6-10 weeks) [3] Doses: 10 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: po (oral gavage) Experimental Results: Tmax (10.8 minutes), Cmax (176.9 nmol/L ), AUC0-∞ (17.4) minutes*μmol/L). For pharmacokinetic study, male wild-type (WT) and Bcrp1 knockout (Bcrp1-/-) FVB mice (6-10 weeks) were fasted for 12 h with free access to water prior to the experiment. Acacetin-7-Glucoside (tilianin) was administered via oral gavage at doses of 10 and 20 mg/kg (n=6 per dose group). Blood samples were collected from the tail vein at pre-dose and at 5, 15, 30, 60, 180, 300, 480, 720, and 1440 min after oral administration. For intravenous administration, Acacetin-7-Glucoside was injected at 2 mg/kg (n=6). Blood samples were collected at pre-dose and at 2, 15, 30, 60, 180, 300, 480, 720, and 1440 min post-dose. Plasma was immediately separated by centrifugation at 5510g for 10 min and stored at -80°C until analysis. [3] |
| ADME/Pharmacokinetics |
After oral administration of Acacetin-7-Glucoside (10 mg/kg) in WT FVB mice: Cmax = 176.9 ± 131.8 nM, AUC0-t = 17.3 ± 16.2 min·μmol/L, MRT = 335.5 ± 185.2 min. In Bcrp1-/- FVB mice: Cmax = 6.6 ± 4.4 nM (significantly lower, ~27-fold), AUC0-t = 1.0 ± 1.2 min·μmol/L (significantly lower, ~17-fold), MRT = 199.5 ± 190.2 min.
After oral administration at 20 mg/kg in WT: Cmax = 203.7 ± 117.4 nM, AUC0-t = 29.0 ± 24.6 min·μmol/L, MRT = 313.3 ± 142.4 min. In Bcrp1-/-: Cmax = 99.2 ± 65.9 nM, AUC0-t = 19.1 ± 8.7 min·μmol/L, MRT = 310.6 ± 192.7 min. After intravenous administration (2 mg/kg) in WT: Cmax = 2017 ± 516 nM, AUC0-t = 134.6 ± 69.9 min·μmol/L, MRT = 133.7 ± 44.1 min. In Bcrp1-/-: Cmax = 3269 ± 707 nM (significantly higher), AUC0-t = 261.1 ± 42.2 min·μmol/L (significantly higher), MRT = 195.2 ± 39.6 min (significantly higher). The absolute oral bioavailability of Acacetin-7-Glucoside was 2.57% (10 mg/kg) and 2.15% (20 mg/kg) in WT FVB mice, versus 0.08% (10 mg/kg) and 0.73% (20 mg/kg) in Bcrp1-/- FVB mice. The major metabolites in mouse plasma were acacetin-7-glucuronide (Aca-7-G) and acacetin-7-sulfate (Aca-7-S). Aca-7-G exhibited the highest systemic exposure in both WT and Bcrp1-/- mice. [3] |
| References | |
| Additional Infomation |
According to reports, tyrianin is found in veratrum, patchouli, and other organisms for which data is available.
Acacetin-7-Glucoside (tilianin) is hydrolyzed to acacetin by intestinal lactase phlorizin hydrolase (LPH). The aglycone acacetin then undergoes extensive phase II metabolism (glucuronidation and sulfation) in vivo. The breast cancer resistance protein (BCRP) significantly impacts the elimination of the sulfated metabolite (acacetin-7-sulfate) in vivo, as evidenced by significantly higher systemic exposure (AUC and Cmax) of Aca-7-S in Bcrp1-/- mice compared to WT mice after both oral and intravenous administration of tilianin. In contrast, BCRP may not be critical for the transport of the parent compound, or other efflux transporters may be overexpressed as compensation in Bcrp1 knockout mice. [3] |
| Molecular Formula |
C22H22O10
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|---|---|
| Molecular Weight |
446.4041
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| Exact Mass |
446.121
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| CAS # |
4291-60-5
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| PubChem CID |
5321954
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| Appearance |
Off-white to light yellow solid
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
754.9±60.0 °C at 760 mmHg
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| Melting Point |
260-262℃
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| Flash Point |
265.5±26.4 °C
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| Vapour Pressure |
0.0±2.7 mmHg at 25°C
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| Index of Refraction |
1.675
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| LogP |
0.66
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
690
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| Defined Atom Stereocenter Count |
5
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| SMILES |
O1[C@]([H])([C@@]([H])([C@]([H])([C@]([H])([C@@]1([H])C([H])([H])O[H])O[H])O[H])O[H])OC1=C([H])C(=C2C(C([H])=C(C3C([H])=C([H])C(=C([H])C=3[H])OC([H])([H])[H])OC2=C1[H])=O)O[H]
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| InChi Key |
NLZCOTZRUWYPTP-MIUGBVLSSA-N
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| InChi Code |
InChI=1S/C22H22O10/c1-29-11-4-2-10(3-5-11)15-8-14(25)18-13(24)6-12(7-16(18)31-15)30-22-21(28)20(27)19(26)17(9-23)32-22/h2-8,17,19-24,26-28H,9H2,1H3/t17-,19-,20+,21-,22-/m1/s
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| Chemical Name |
5-hydroxy-2-(4-methoxyphenyl)-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one
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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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~50 mg/mL (~112.01 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.66 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 20.8 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 2: ≥ 2.08 mg/mL (4.66 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 20.8 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 | 2.2401 mL | 11.2007 mL | 22.4014 mL | |
| 5 mM | 0.4480 mL | 2.2401 mL | 4.4803 mL | |
| 10 mM | 0.2240 mL | 1.1201 mL | 2.2401 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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