VS-5584 (SB2343)

Catalog No.S7016 Batch:S701601

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Technical Data

Formula

C17H22N8O
Molecular Weight 354.41 CAS No. 1246560-33-7
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)
Homogeneous suspension
0.5% methylcellulose 0.2% Tween 80
10.0mg/ml Taking the 1 mL working solution as an example, take 10 mg of this product, add it to 1 ml of 0.5% methylcellulose+0.2% Tween 80 clear solution, and mix evenly to make it a uniform suspension. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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.
Targets
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]

Protocol (from reference)

Kinase Assay:[2]
  • 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 Assay:[2]
  • 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
Animal Study:[2]
  • Animal Models

    Male (PC3 and COLO 205) or female (MV4-11 and HuH7) BALB/c nude mice or female SCID mice (NCI-N87)

  • Dosages

    11 mg/kg, 25 mg/kg once daily

  • Administration

    orally

Customer Product Validation

, , Platelets, 2017, 29(3):277-287

Data from [Data independently produced by , , Cell Physiol Biochem, 2018, 47(2):680-693]

Data from [Data independently produced by , , Biomed Pharmacother, 2018, 428-437]

Data from [Data independently produced by , , PLoS One, 2015, 10(7):e0132655.]

Selleck's VS-5584 (SB2343) has been cited by 18 publications

Identification of small-molecule protein-protein interaction inhibitors for NKG2D [ Proc Natl Acad Sci U S A, 2023, 120(18):e2216342120] PubMed: 37098070
Selectively Targeting Breast Cancer Stem Cells by 8-Quinolinol and Niclosamide [ Int J Mol Sci, 2022, 23(19)11760] PubMed: 36233074
Selectively Targeting Breast Cancer Stem Cells by 8-Quinolinol and Niclosamide [ Int J Mol Sci, 2022, 23(19)11760] PubMed: 36233074
Therapeutic Targeting of Stromal-Tumor HGF-MET Signaling in an Organotypic Triple-Negative Breast Tumor Model [ Mol Cancer Res, 2022, 20(7):1166-1177] PubMed: 35348758
Therapeutic Targeting of Cancer Stem Cells Prevents Resistance of Colorectal Cancer Cells to MEK Inhibition [ ACS Pharmacol Transl Sci, 2022, 5(9):724-734] PubMed: 36110381
PI3K/mTOR dual-inhibition with VS-5584 enhances anti-leukemic efficacy of ponatinib in blasts and Ph-negative LSCs of chronic myeloid leukemia [ Eur J Pharmacol, 2021, 910:174446] PubMed: 34461124
Antitumor activity and mechanism of resistance of the novel HDAC and PI3K dual inhibitor CUDC-907 in pancreatic cancer [ Cancer Chemother Pharmacol, 2021, 10.1007/s00280-020-04210-0] PubMed: 33392641
CCT128930 induces G1-phase arrest and apoptosis and synergistically enhances the anticancer efficiency of VS5584 in human osteosarcoma cells [ Biomed Pharmacother, 2020, 130:110544] PubMed: 32721630
VS-5584, a PI3K/mTOR dual inhibitor, exerts antitumor effects on neuroblastomas in vitro and in vivo [ J Pediatr Surg, 2020, S0022-3468(20)30786-7] PubMed: 33189297
New High-Throughput Screening Identifies Compounds That Reduce Viability Specifically in Liver Cancer Cells That Express High Levels of SALL4 by Inhibiting Oxidative Phosphorylation. [ Gastroenterology, 2019, 157(6):1615-1629] PubMed: 31446059

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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