1. Autophagy Neuronal Signaling
  2. Mitophagy PINK1/Parkin Amyloid-β
  3. Y040-7904

Y040-7904  (Synonyms: 7-(β-D-Galactopyranosyloxy)-4-phenylchromen-2-one)

Cat. No.: HY-174806 Purity: 99.36%
Handling Instructions Technical Support

Y040-7904 is a mitophagy activator. Y040-7904 enhances mitophagy by promoting mitochondria transport to autophagosomes and the fusion of autophagosomes with autolysosomes. Y040-7904 induces mitophagy through the SIRT1/FoxO3 pathway. Y040-7904 upregulates the levels of Parkin, PINK1, and LC3II/I. Y040-7904 reduces amyloid-β () accumulation in both in vitro and in vivo models of Alzheimer’s disease.

For research use only. We do not sell to patients.

Y040-7904

Y040-7904 Chemical Structure

CAS No. : 889662-19-5

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10 mM * 1 mL in DMSO
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Description

Y040-7904 is a mitophagy activator. Y040-7904 enhances mitophagy by promoting mitochondria transport to autophagosomes and the fusion of autophagosomes with autolysosomes. Y040-7904 induces mitophagy through the SIRT1/FoxO3 pathway. Y040-7904 upregulates the levels of Parkin, PINK1, and LC3II/I. Y040-7904 reduces amyloid-β () accumulation in both in vitro and in vivo models of Alzheimer’s disease[1].

In Vitro

Y040-7904 (20 μM, 24 h) induces a detectable increase in mitolysosomes and increases the proportions of mitophagosomes (9%) and mitolysosomes (18%), higher than those induced by the two established mitophagy inducers, Urolithin A (HY-100599) and UMI-77 (HY-18628), in HT22 cells[1].

Y040-7904 (5-20 μM, 24 h) facilitates the expression of mitophagy-related proteins PINK1 and Parkin through the SIRT1-FoxO3a pathway, ultimately resulting in an elevation in mitophagy levels in HT22 cells and N2a/APPswe cells[1].

Y040-7904 (5-20 μM, 24 h) enhances mitochondrial biogenesis by upregulateing the expression of MFN2, TIM23, and TOM20 in HT22 cells[1].

Y040-7904 (5-20 μM, 24 h) mitigates APP and Aβ1-42 accumulation in N2a/APPswe cells[1].

Y040-7904 (5-20 μM, 24 h) upregulates the levels of Parkin, PINK1, and LC3II/I in N2a/APPswe cells[1].

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

Western Blot Analysis[1]

Cell Line: HT22 cells, PINK1 silenced HT22 cells
Concentration: 5, 10, and 20 μM
Incubation Time: 24 h
Result: Increased the levels of mitophagy-related proteins, including PINK1, Parkin, phosphorylated Ser65-ubiquitin (pUb), and LC3B-II/LC3B–I in a dose- and time-dependent manner in HT22 cells.
Abolished the increase in mitophagy-related proteins, such as pUb and LC3 in PINK1 silenced HT22 cells.
Increased nuclear FoxO3a levels, accompanied by a concomitant decrease in cytoplasmic FoxO3a levels in HT22 cells.
Increased levels of mitochondrial marker MFN2, TIM23, and TOM20 in HT22 cells.

Western Blot Analysis[1]

Cell Line: Neuron-2a cells (N2a/APPswe cells)
Concentration: 5, 10, and 20 μM
Incubation Time: 24 h
Result: Significantly reduced the levels of APP and its C-terminal fragment C99 decreased intracellular Aβ1-42 levels in a dose-dependent manner in N2a/APPswe cells.
Significantly upregulated the levels of f Parkin, PINK1, and LC3II/I in N2a/APPswe cells.

Immunofluorescence[1]

Cell Line: HT22 cells
Concentration: 20 μM
Incubation Time: 24 h
Result: Significantly promoted the nuclear localization of FoxO3a.
In Vivo

Y040-7904 (500-1000 μM, 96 h) holds therapeutic potential for mitigating Alzheimer’s disease pathology in CL4176 and CL2006 worms[1].

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

Animal Model: Transgenic C. elegans strains CL417647 and CL2006[1].
Dosage: 500, 1000 μM
Administration: 96 h
Result: Resulted in a dose-dependent reduction in Aβ1-42 levels in CL4176 worms.
Decreased the paralysis rate of CL4176 worms (76.2%, 1000 μM), compared to 89.5% in untreated worm at 30 h post temperature upshift.
Reduced paralysis rate of CL2006 worms by 29.3% compared to untreated controls.
Molecular Weight

370.35

Formula

C20H18O7

CAS No.
Appearance

Solid

Color

White to off-white

SMILES

O=C1C=C(C2=CC=CC=C2)C3=CC=C(O[C@H]4[C@@H]([C@H]([C@@H](CO4)O)O)O)C=C3O1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (270.01 mM; ultrasonic and warming and heat to 60°C; 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 2.7001 mL 13.5007 mL 27.0015 mL
5 mM 0.5400 mL 2.7001 mL 5.4003 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 (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

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

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

This equation is commonly abbreviated as: C1V1 = C2V2

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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: ≥ 5 mg/mL (13.50 mM); Clear solution

    This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 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: ≥ 5 mg/mL (13.50 mM); Clear solution

    This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 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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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
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+
%
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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 (sealed storage, away from moisture)

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
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 (sealed storage, away from moisture). 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 2.7001 mL 13.5007 mL 27.0015 mL 67.5037 mL
5 mM 0.5400 mL 2.7001 mL 5.4003 mL 13.5007 mL
10 mM 0.2700 mL 1.3501 mL 2.7001 mL 6.7504 mL
15 mM 0.1800 mL 0.9000 mL 1.8001 mL 4.5002 mL
20 mM 0.1350 mL 0.6750 mL 1.3501 mL 3.3752 mL
25 mM 0.1080 mL 0.5400 mL 1.0801 mL 2.7001 mL
30 mM 0.0900 mL 0.4500 mL 0.9000 mL 2.2501 mL
40 mM 0.0675 mL 0.3375 mL 0.6750 mL 1.6876 mL
50 mM 0.0540 mL 0.2700 mL 0.5400 mL 1.3501 mL
60 mM 0.0450 mL 0.2250 mL 0.4500 mL 1.1251 mL
80 mM 0.0338 mL 0.1688 mL 0.3375 mL 0.8438 mL
100 mM 0.0270 mL 0.1350 mL 0.2700 mL 0.6750 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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Y040-7904
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