VS-5584 (SB2343)

Catalog No.S7016

VS-5584 (SB2343) Chemical Structure

Molecular Weight(MW): 354.41

VS-5584 (SB2343) is a potent and selective dual PI3K/mTOR inhibitor for mTOR, PI3Kα/β/δ/γ with IC50 of 3.4 nM and 2.6-21 nM, respectively. Phase 1.

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2 Customer Reviews

  • VS-5584 inhibits melanoma cell survival and proliferation-Established melanoma cell lines (A375, A-2058 and SK-MEL-3), patient-derived primary melanoma cells, B10BR melanocytes and primary human keratinocytes (“Kera”) were treated with applied concentration of VS-5585 (“VS”) or vehicle control (“C”, 0.1% of DMSO), cell survival was tested by MTT assay (A, E and F) and trypan blue exclusion assay (B, for A375 cells); Cell proliferation was analyzed by through [H3] Thymidine incorporation assay (C, for A375 cells) and clonogenicity assay (D, for A375 cells). Data were expressed as mean ± SD, experiments were repeated three times. *p<0.05 vs group “C”.

    PLoS One, 2015, 10(7):e0132655.. VS-5584 (SB2343) purchased from Selleck.

    Effect of VS-5584 on platelet adhesion. A-F: WP (A, B) and PRP (D, E) were treated with DMSO as vehicle (A, D; n = 3) or with 20 nM (B; n = 3) and 20 μM (E; n = 3) of VS-5584 and seeded on siliconized coverslips for the quantitative analysis of WP (C) and PRP adhesion (F). Scale bars: A, B, D, E = 50 μm; Data are given in % of vehicle. Mean ± SEM. *p < 0.05 vs. vehicle. G, H: Representative images of WP treated with vehicle (G) or 20 nM of VS-5584 (H). The number of non-spread cells (arrows) is higher in VS-5584-treated WP. Scale bars: 20 μm. I: Quantification of spread platelets based on their morphology. Data are given in % of vehicle. Mean ± SEM. *p < 0.05 vs. vehicle.

    Platelets, 2017, 29(3):277-287. VS-5584 (SB2343) purchased from Selleck.

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Biological Activity

Description VS-5584 (SB2343) is a potent and selective dual PI3K/mTOR inhibitor for mTOR, PI3Kα/β/δ/γ with IC50 of 3.4 nM and 2.6-21 nM, respectively. Phase 1.
PI3Kα [1]
(Cell-free assay)
PI3Kδ [1]
(Cell-free assay)
PI3Kγ [1]
(Cell-free assay)
mTOR [1]
(Cell-free assay)
PI3Kβ [1]
(Cell-free assay)
2.6 nM 2.7 nM 3.0 nM 3.4 nM 21 nM
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 is approximately 10-fold selective for cancer stem cells with an EC50 of 15 nM in HMLE breast cancer cells. VS-5584 preferentially decreases CD44Hi/CD24Lo cells in an HMLER immortalized mammary cancer cell line. In SUM159 cells, VS-5584 effectively eliminates the cancer stem cell side population. [1] A large human cancer cell line panel screen (436 lines) reveals broad antiproliferative sensitivity and that cells harboring mutations in PI3KCA are generally more sensitive toward VS-5584 treatment. In the FLT3-ITD harboring MV4-11 cells, VS-5584 blocks pAkt (S473) and pAkt (T308) with IC50 of 12 and 13 nM, respectively. The IC50 of VS-5584 for pS6 (S240/244), pAkt (S473), and pAkt (T308) are 20, 23, and 15 nM, respectively. [2]

In vivo In mice bearing triple negative breast cancer tumors, oral dosing of VS-5584 decreases tumor cancer stem cells and induces tumor regression in taxane-resistant models. [1] In a PTENnull human prostate PC3 xenograft model, treatment with VS-5584 leads to significant tumor growth inhibition (TGI) of 79% and 113% for 11 and 25 mg/kg, respectively. In a FLT3-ITD AML xenograft model, VS-5584 treatment induces dose-dependent inhibition of tumor growth (28% for 3.7 mg/kg and 76% for 11 mg/kg). [2]


Kinase Assay:[2]
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In vitro mTOR kinase assays :

The reaction mixture consisted of the following components in 10 μL assay buffer (50 mM Hepes pH 7.5, 10 mM MgCl 2, 3 mM MnCl 2, 1 mM EGTA, 2 mM DTT, 0.01%Tween-20): 0.10 μg/mL of in-house generated mTOR enzyme, 0.05 μM ULight-eIF4E-binding protein 1 (Thr37/46) peptide and 10 μM ATP. The mixture is incubated for 60 min at room temperature. 10 μL of Detection mixture consisted of 16 mM EDTA, 0.004 mM Eu-W1024-labeled Anti-Phospho-eIF4E-binding protein 1-(Thr37/46) antibody and 1X LANCE® Detection Buffer is then added and incubated for 60 min.
Cell Research:[2]
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  • Cell lines: SNU-478, SNU-1196, SNU-245, SNU-1079, SNU-308, and SNU-869
  • Concentrations: ~10 μM
  • Incubation Time: 48 h
  • Method: CellTiter-Glo assay
    (Only for Reference)
Animal Research:[2]
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  • Animal Models: Male (PC3 and COLO 205) or female (MV4-11 and HuH7) BALB/c nude mice or female SCID mice (NCI-N87)
  • Formulation: 0.5% methylcellulose (w/v) and 0.1% Tween-80 in H2O (MC/Tween)
  • Dosages: 11 mg/kg, 25 mg/kg once daily
  • Administration: orally
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 71 mg/mL (200.33 mM)
Ethanol 3 mg/mL (8.46 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
0.5% methylcellulose+0.2% Tween 80
For best results, use promptly after mixing.
30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 354.41


CAS No. 1246560-33-7
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02372227 Terminated Relapsed Malignant Mesothelioma Verastem Inc. January 2015 Phase 1
NCT01991938 Terminated Non Hematologic Cancers|Metastatic Cancer|Lymphoma Verastem Inc. November 2013 Phase 1

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID