Home PI3K/Akt/mTOR PI3K inhibitor VS-5584 (SB2343) For research use only.

VS-5584 (SB2343)

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.

VS-5584 (SB2343) Chemical Structure

VS-5584 (SB2343) Chemical Structure

CAS No. 1246560-33-7

Purity & Quality Control

Batch: S701601 DMSO]71 mg/mL]false]Ethanol]3 mg/mL]false]Water]Insoluble]false Purity: 99.92%
99.92

VS-5584 (SB2343) Related Products

Signaling Pathway

PI3K Signaling Pathways

PI3K Signaling Pathway

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
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]
Kinase Assay 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 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
In Vivo
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]
Animal Research 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
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

Chemical Information & Solubility

Molecular Weight 354.41 Formula

C17H22N8O
CAS No. 1246560-33-7 SDF --
Smiles CC1=NC2=C(N=C(N=C2N1C(C)C)N3CCOCC3)C4=CN=C(N=C4)N
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 71 mg/mL ( (200.33 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 3 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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