Home PI3K/Akt/mTOR PI3K inhibitor VS-5584 (SB2343)

research use only

VS-5584 (SB2343) PI3K inhibitor

Cat.No.S7016

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. This compound is in Phase 1.
VS-5584 (SB2343) PI3K inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 354.41

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

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

Chemical Information, Storage & Stability

Molecular Weight 354.41 Formula

C17H22N8O

 Storage (From the date of receipt)
CAS No. 1246560-33-7 -- Storage of Stock Solutions

Synonyms N/A Smiles CC1=NC2=C(N=C(N=C2N1C(C)C)N3CCOCC3)C4=CN=C(N=C4)N

Solubility

In vitro
Batch:

DMSO : 71 mg/mL (200.33 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 3 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC50/Ki
PI3Kα [1]
(Cell-free assay)
2.6 nM
PI3Kδ [1]
(Cell-free assay)
2.7 nM
PI3Kγ [1]
(Cell-free assay)
3.0 nM
mTOR [1]
(Cell-free assay)
3.4 nM
PI3Kβ [1]
(Cell-free assay)
21 nM
In vitro
VS-5584 (SB2343) 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. It is approximately 10-fold selective for cancer stem cells with an EC50 of 15 nM in HMLE breast cancer cells. This compound preferentially decreases CD44Hi/CD24Lo cells in an HMLER immortalized mammary cancer cell line. In SUM159 cells, it 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, it blocks pAkt (S473) and pAkt (T308) with IC50 of 12 and 13 nM, respectively. The IC50 of this compound 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 for VS-5584 (SB2343) 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.
In vivo
In mice bearing triple negative breast cancer tumors, oral dosing of S7016 decreases tumor cancer stem cells and induces tumor regression in taxane-resistant models. [1] In a PTENnull human prostate PC3 xenograft model, treatment with S7016 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, S7016 treatment induces dose-dependent inhibition of tumor growth (28% for 3.7 mg/kg and 76% for 11 mg/kg). [2]
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.

Signaling Pathway Map