1. PI3K/Akt/mTOR MAPK/ERK Pathway Anti-infection
  2. mTOR Ribosomal S6 Kinase (RSK) Bacterial
  3. Zederone

Zederone is a sesquiterpene. Zederone inhibits ovarian cancer cell proliferation through mTOR/p70s6K signalling pathway. Zederone inhibits CYP activities with IC50s of 2.9 μM (CYP2B6), 9.2 μM (CYP2C9), 11,2 μM (CYP2C19) and >30 μM (CYP1A2 and CYP2D6). Zederone is hepatotoxic with LD50 value at 24 hours in mice of approximately 223 mg/kg and cytotoxic against the KG1a cell line. Zederone shows antibacterial activity against a number of multi-drug resistant and Methicillin (HY-121544)-resistant Staphylococcus aureus strain. Zederone shows cognition improving capacity and assists in the modulation of gut bacterial dysbiosis.

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Zederone

Zederone Chemical Structure

CAS No. : 7727-79-9

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  • Biological Activity

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Description

Zederone is a sesquiterpene. Zederone inhibits ovarian cancer cell proliferation through mTOR/p70s6K signalling pathway. Zederone inhibits CYP activities with IC50s of 2.9 μM (CYP2B6), 9.2 μM (CYP2C9), 11,2 μM (CYP2C19) and >30 μM (CYP1A2 and CYP2D6). Zederone is hepatotoxic with LD50 value at 24 hours in mice of approximately 223 mg/kg and cytotoxic against the KG1a cell line. Zederone shows antibacterial activity against a number of multi-drug resistant and Methicillin (HY-121544)-resistant Staphylococcus aureus strain. Zederone shows cognition improving capacity and assists in the modulation of gut bacterial dysbiosis[1][2][3][4][5][6].

IC50 & Target[2]

mTOR

 

In Vitro

Zederone (0-80 μg/mL, 24 h) can inhibit the proliferation of human ovarian cancer cell line SKOV3 and arrest SKOV3 cells at G1 phase, and it may regulate the proliferation of SKOV3 cells through inhibiting mTOR/p70s6K signalling pathway[2].
Zederone (0-30 μM, 24 h) significantly activates mouse PXR, significantly activates human PXR and CAR, and AhR shows no response in human hepatoma C3A cells[3].
Zederone exhibits IC50s in HLM incubations of 3.9 μM (CYP2B6), 9.9 μM (CYP3A4/M) and >50 μM (CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4/T)[3].
Zederone shows antibacterial activity against SA1199B, ATCC25923, XU212, RN4220 and EMRSA15 with MICs of 128, 64, 128, 64 and 128 μg/ml[4].
Zederone (0-100 μg/mL, 48 h) selectively kills leukemia stem cells (KG1a) with an IC50 of 56.8 μg/mL and low cytotoxicity toward normal peripheral blood mononuclear cells (PBMCs) [5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay[2]

Cell Line: SKOV3 cells and IOSE80 cells
Concentration: 0, 5, 10, 20, 40 and 80 μg/mL
Incubation Time: 24 h
Result: Inhibited the proliferation of SKOV3 cells in a dose-dependent manner but had no significant effect on the proliferation of IOSE80 cells.

Cell Cycle Analysis[2]

Cell Line: SKOV3 cells
Concentration: 10, 20, 40 μg/mL
Incubation Time: 24 h
Result: Significantly increased the ratio of G1 phase cells, while the ratio of S phase cells and G2/M phase cells was significantly decreased.

Western Blot Analysis[2]

Cell Line: SKOV3 cells
Concentration: 10, 20, 40 μg/mL
Incubation Time: 24 h
Result: Significantly decreased the expression levels of p-mTOR, p-p70s6K, mTOR and p70s6K.
Maintained the expression levels of p-PI3K and p-Akt.
In Vivo

Zederone (50-300 mg/kg, i.p., single dose) increases the expression of cytochrome P450 (Cyp) and leads to the formation of biological reactive metabolites and that cause the oxidative stress and liver cell injuries in mice[1].
Zederone (10 mg/kg, p.o.) improves the fecal microbial profile in dementia induced rat model, showing a increased shift towards Lactobacillus genera from Bacteroides[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Acute liver toxicity model established in adult male ICR mice weighing 30 to 35 g (approximately 6-8 weeks of age)[1]
Dosage: 50, 100, 150, 200, and 300 mg/kg
Administration: Intraperitoneal injection (i.p.), single dose
Result: Induced liver enlargement with scattered white foci over the organ.
Observed hepatic centrilobular necrosis with marked increases in plasma alanine transaminase activity and total bilirubin levels.
Decreased the activity of superoxide dismutase and the hepatic glutathione content at 200 mg/kg.
Increased the messenger RNA (mRNA) expression of Cyp2b10 and Cyp3a11 and proinflammatory cytokine tumor necrosis factor, and decreased the nuclear factor-E2-related factor 2 protein at 200 mg/kg.
Molecular Weight

246.30

Formula

C15H18O3

CAS No.
Appearance

Solid

Color

White to yellow

SMILES

CC1=COC(C/C(C)=C/CC[C@]2(C)[C@@]3([H])O2)=C1C3=O

Structure Classification
Initial Source
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

-20°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

Solvent & Solubility
In Vitro: 

DMSO : 50 mg/mL (203.00 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 4.0601 mL 20.3004 mL 40.6009 mL
5 mM 0.8120 mL 4.0601 mL 8.1202 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
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Concentration
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Volume
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Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

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Volume (start)

V1

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Concentration (final)

C2

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Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2.5 mg/mL (10.15 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.5 mg/mL (10.15 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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Animal weight
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g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation

Purity: 99.61%

References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 4.0601 mL 20.3004 mL 40.6009 mL 101.5022 mL
5 mM 0.8120 mL 4.0601 mL 8.1202 mL 20.3004 mL
10 mM 0.4060 mL 2.0300 mL 4.0601 mL 10.1502 mL
15 mM 0.2707 mL 1.3534 mL 2.7067 mL 6.7668 mL
20 mM 0.2030 mL 1.0150 mL 2.0300 mL 5.0751 mL
25 mM 0.1624 mL 0.8120 mL 1.6240 mL 4.0601 mL
30 mM 0.1353 mL 0.6767 mL 1.3534 mL 3.3834 mL
40 mM 0.1015 mL 0.5075 mL 1.0150 mL 2.5376 mL
50 mM 0.0812 mL 0.4060 mL 0.8120 mL 2.0300 mL
60 mM 0.0677 mL 0.3383 mL 0.6767 mL 1.6917 mL
80 mM 0.0508 mL 0.2538 mL 0.5075 mL 1.2688 mL
100 mM 0.0406 mL 0.2030 mL 0.4060 mL 1.0150 mL
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  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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