1. PI3K/Akt/mTOR Autophagy
  2. PI3K Autophagy
  3. Vps34-PIK-III

Vps34-PIK-III is an orally active and selective VPS34 inhibitor (IC50=18 nM). Vps34-PIK-III effectively inhibits autophagy and can be used as a molecular tool. vps34-PIK-III is also a PI3K inhibitor that inhibits the expression of genes in liver cancer stem cells (CSCs).

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Vps34-PIK-III Chemical Structure

Vps34-PIK-III Chemical Structure

CAS No. : 1383716-40-2

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10 mM * 1 mL in DMSO
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Customer Review

Based on 4 publication(s) in Google Scholar

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Description

Vps34-PIK-III is an orally active and selective VPS34 inhibitor (IC50=18 nM). Vps34-PIK-III effectively inhibits autophagy and can be used as a molecular tool. vps34-PIK-III is also a PI3K inhibitor that inhibits the expression of genes in liver cancer stem cells (CSCs)[1][2][3].

IC50 & Target[2]

Vps34

18 nM (IC50)

PI(3)Kδ

1.2 μM (IC50)

PI(3)Kγ

3.04 μM (IC50)

PI(3)Kα

3.96 μM (IC50)

In Vitro

Vps34-PIK-III (1, 5, 10 μM; 24 h) inhibits autophagy and LC3 lipidation in DLD1 cells[1].
Vps34-PIK-III (1, 5, 10 μM; 24 h) leads to an increase in the lipidated and nonlipidated forms of LC3 in DLD1 cells[1].
Vps34-PIK-III (5 μM; 24 h) significantly decreases the expression of stemness genes in HCC cells[2].
Vps34-PIK-III (5 μM; 24 h) suppresses liver CSCs via AMPK activation in Huh7 and MHCC97H cells[2].

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

Cell Viability Assay[1]

Cell Line: DLD1 cells
Concentration: 1, 5, 10 µM
Incubation Time: 24 h
Result: Prevented the degradation of autophagy substrates p62, NCOA4, NBR1, NDP52, and FTH1.

RT-PCR[1]

Cell Line: HCC cells
Concentration: 5 µM
Incubation Time: 24 h
Result: Inhibited stemness genes expression.

Western Blot Analysis[1]

Cell Line: Huh7 and MHCC97H cells
Concentration: 5 µM
Incubation Time: 24 h
Result: Inhibited liver CSCs by activating AMPK.
In Vivo

Vps34-PIK-III (10 mg/kg; p.o.; single) rapidly absorbed and shows moderate mean systemic clearance (30 mL/min/kg, approximately 33% of hepatic blood flow), with good oral bioavailability (F% = 47)[1].

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

Animal Model: C57BL/6 mice[1].
Dosage: 10 mg/kg; 2 mg/kg
Administration: Oral administration; intravenous injection; single
Result: 1.19 Pharmacokinetic Parameters of Vps34-PIK-III in C57BL/6 mice[1].
IV (2 mg/kg) PO (10 mg/kg)
Tmax (h) 0.7
Cmax (nM) 2994
AUCinf (nM•h) 2855 6725
t1/2 (h) 1.2
CL (mL/min/kg) 30
Vdss (L/kg) 1.5
F (%) 47%
Molecular Weight

319.36

Formula

C17H17N7

CAS No.
Appearance

Solid

Color

White to off-white

SMILES

NC1=NC=C(C2=CC=NC(NC3=CC=NC=C3)=N2)C(CC4CC4)=N1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
Solvent & Solubility
In Vitro: 

DMSO : ≥ 31 mg/mL (97.07 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

*"≥" means soluble, but saturation unknown.

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 3.1313 mL 15.6563 mL 31.3126 mL
5 mM 0.6263 mL 3.1313 mL 6.2625 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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

  • Molarity Calculator

  • Dilution Calculator

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: ≥ 2.5 mg/mL (7.83 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 (7.83 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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(per animal)

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
+
%
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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).
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, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 3.1313 mL 15.6563 mL 31.3126 mL 78.2816 mL
5 mM 0.6263 mL 3.1313 mL 6.2625 mL 15.6563 mL
10 mM 0.3131 mL 1.5656 mL 3.1313 mL 7.8282 mL
15 mM 0.2088 mL 1.0438 mL 2.0875 mL 5.2188 mL
20 mM 0.1566 mL 0.7828 mL 1.5656 mL 3.9141 mL
25 mM 0.1253 mL 0.6263 mL 1.2525 mL 3.1313 mL
30 mM 0.1044 mL 0.5219 mL 1.0438 mL 2.6094 mL
40 mM 0.0783 mL 0.3914 mL 0.7828 mL 1.9570 mL
50 mM 0.0626 mL 0.3131 mL 0.6263 mL 1.5656 mL
60 mM 0.0522 mL 0.2609 mL 0.5219 mL 1.3047 mL
80 mM 0.0391 mL 0.1957 mL 0.3914 mL 0.9785 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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