2. PI3K/Akt/mTOR
  3. PI3K mTOR
  4. VS-5584

VS-5584 is a pan-PI3K/mTOR kinase inhibitor with IC50s of 16 nM, 68 nM, 42 nM, 25 nM, and 37 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR, respectively. VS-5584 simultaneously blocks mTORC2 as well as mTORC1.

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

VS-5584 Chemical Structure

VS-5584 Chemical Structure

CAS No. : 1246560-33-7

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Solid + Solvent
10 mM * 1 mL in DMSO
ready for reconstitution
 USD 109 In-stock
Solution
10 mM * 1 mL in DMSO USD 109 In-stock
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5 mg USD 99 In-stock
10 mg USD 132 In-stock
50 mg USD 440 In-stock
100 mg USD 715 In-stock
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Customer Review

Based on 5 publication(s) in Google Scholar

VS-5584 Related Antibodies

Top Publications Citing Use of Products

View All PI3K Isoform Specific Products:

View All Isoforms
PI3Kα PI3Kβ PI3Kγ PI3Kδ PI3KC2α PI3KC2β PI3KC2γ Vps34 PI3K PI3KC3 p120γ

View All mTOR Isoform Specific Products:

View All Isoforms
mTOR mTORC1 mTORC2

  • Biological Activity

  • Protocol

  • Purity & Documentation

  • References

  • Customer Review

Description

VS-5584 is a pan-PI3K/mTOR kinase inhibitor with IC50s of 16 nM, 68 nM, 42 nM, 25 nM, and 37 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ and mTOR, respectively. VS-5584 simultaneously blocks mTORC2 as well as mTORC1.

IC50 & Target[1]

PI3Kα

16 nM (IC50)

PI3Kγ

25 nM (IC50)

PI3Kδ

42 nM (IC50)

PI3Kβ

68 nM (IC50)

Vps34

7470 nM (IC50)

mTOR

37 nM (IC50)

mTORC1

 

mTORC2

 

DNA-PK

1270 nM (IC50)

In Vitro

VS-5584 is an ATP-competitive inhibitor which selectively inhibits PI3K/mTOR signaling with equivalent low nanomolar potency against all human Class I PI3K isoforms and mTOR kinase. VS-5584 (0.001, 0.01, 0.1,1,10 and 100 μM) preferentially inhibits cancer stem cells in HMLE breast cancer cells while Paclitaxel increases the percentage of cancer stem cells. VS-5584 (0.1, 1, 10, 100 and 1000 nM) reduces the number of Aldefluor-positive cancer stem cells while Paclitaxel increases the percentage of cancer stem cells. VS-5584 (10, 30, 100, 300 nM) reduces the percentage of cancer stem cells (side population) in a Hoechst dye exclusion assay[1]. VS-5584 is a potent inhibitor of mTOR (IC50=37 nM) as well as class I PI3K isoforms (IC50: PI3Kα=16 nM; PI3Kβ=68 nM; PI3Kγ=25 nM; PI3Kδ=42 nM). All other evaluated kinases show negligible binding when tested up to 10 μM VS-5584[1].

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

VS-5584 Related Antibodies
In Vivo

Nude mice bearing MDA-MB-231 human breast cancer tumors are treated for 5 days with once daily oral VS-5584 (25 mg/kg). Oral treatment of tumor bearing mice with VS-5584 reduces cancer atem cells analyzed from extracted tumors. Mice are implanted with tumor fragments from a docetaxel-resistant patient-derived triple negative breast cancer. Mice are treated with VS-5584 (20 mg/kg, po, qd) or Docetaxel (20 mg/kg, i.v.). Oral VS-5584 induces tumor regression in a Docetaxel-resistant patient-derived breast cancer model[1]. A single oral dose of VS-5584 is rapidly absorbed with a tmax of 0.9 hours and an elimination half-life of 10 hours. To determine the pharmacokinetic and pharmacodynamic relationship in tumors, PC3-tumor–bearing mice are treated with a single dose of VS-5584 and plasma and tumors are harvested after 6 hours and analyzed for concentrations of VS-5584 and effects on target efficacy biomarkers. Plasma levels of VS-5584 increase dose-dependently. For evaluation of efficacy in a Rapamycin-sensitive PC3 engraftment model, tumor-bearing mice are treated with VS-5584 for 28 days in comparison with the rapalog Everolimus. VS-5584 is well tolerated at both doses tested (11 and 25 mg/kg) with minimal weight loss (mean 4.7% on day 27). Treatment with VS-5584 leads to significant tumor growth inhibition (TGI) of 79% and 113% for 11 and 25 mg/kg, respectively[1].

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

354.41

Formula

C17H22N8O
CAS No.
Appearance

Solid

Color

Light yellow to yellow

SMILES

NC1=NC=C(C2=C3N=C(C)N(C(C)C)C3=NC(N4CCOCC4)=N2)C=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 : 33.33 mg/mL (94.04 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 2.8216 mL 14.1080 mL 28.2159 mL
5 mM 0.5643 mL 2.8216 mL 5.6432 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)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

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

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
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 (7.05 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 (7.05 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:

Dosage

mg/kg

Animal weight
(per animal)

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).
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: 99.14%

COA (252 KB) LCMS (97 KB)

Handling Instructions (2659 KB)
References
Cell Assay
[1]

For proliferation assays in 96-well plates, SET-2, SNU-478, SNU-1196, SNU-245, SNU-1079, SNU-308, SNU-869, and MKN7 cells are used. The multiple myeloma cells (H929, MM1.S, MM1.R, R8226, U266) and nasopharyngeal cells (CNE-1, CNE-2, HONE1, HK1) are used. Cells are seeded at 30% to 50% confluency for adherent cells, or 2,000 to 6,000 cells for suspension cells and treated the following day with VS-5584 (in triplicates) at concentrations up to 10 μM for 48 hours. Cell viability is monitored using the CellTiter-Glo assay. Dose-response curves were plotted to determine IC50 values for the compounds using the XL-fit software[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

Mice[1]
Athymic BALB/c nude mice (BALB/cOlaHsd-Foxn1nu) are used. Fox-Chase severe combined immunodeficient (SCID) mice (CB17/Icr-Prkdcscid/CrlBltw) are used. Male (PC3 and COLO 205) or female (MV4-11 and HuH7) BALB/c nude mice or female SCID mice (NCI-N87) are implanted intradermally in the right flank with 5×106 (PC3, COLO205, HuH7, NCI-N87) or 1×107 (MV4-11) cells. Cells are resuspended in 70% (v/v; COLO205 and HuH7 only) or 50% (v/v) serum-free growth medium/Matrigel and injected in a total volume of 100 μL, using a 27.5-gauge needle. Dosing started 7 to 14 days after tumor implantation. VS-5584 (11 and 25 mg/kg) is dosed daily orally[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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 2.8216 mL 14.1080 mL 28.2159 mL 70.5398 mL
5 mM 0.5643 mL 2.8216 mL 5.6432 mL 14.1080 mL
10 mM 0.2822 mL 1.4108 mL 2.8216 mL 7.0540 mL
15 mM 0.1881 mL 0.9405 mL 1.8811 mL 4.7027 mL
20 mM 0.1411 mL 0.7054 mL 1.4108 mL 3.5270 mL
25 mM 0.1129 mL 0.5643 mL 1.1286 mL 2.8216 mL
30 mM 0.0941 mL 0.4703 mL 0.9405 mL 2.3513 mL
40 mM 0.0705 mL 0.3527 mL 0.7054 mL 1.7635 mL
50 mM 0.0564 mL 0.2822 mL 0.5643 mL 1.4108 mL
60 mM 0.0470 mL 0.2351 mL 0.4703 mL 1.1757 mL
80 mM 0.0353 mL 0.1763 mL 0.3527 mL 0.8817 mL
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VS-5584 Related Classifications

Help & FAQs
  • 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.

Keywords:

VS-55841246560-33-7SB2343VS5584VS 5584SB 2343SB-2343PI3KmTORPhosphoinositide 3-kinaseMammalian target of RapamycinInhibitorinhibitorinhibit

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