Name: VS-5584 (SB2343)
Brand: Selleck Chemicals
SKU: S7016
Rating: 5 (15 reviews)

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Quality Control

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

Cited in Nature Medicine for its top-tier quality
COA
NMR
HPLC
SDS
Datasheet

99.92

Related Targets	Akt mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Other PI3K Inhibitors	GDC-0077 (Inavolisib) SAR405 Quercetin (Sophoretin) LY294002 XL147 analogue Tersolisib (STX-478) Buparlisib (BKM120) 740 Y-P (PDGFR 740Y-P) GO-203 TFA Eganelisib (IPI-549)

Chemical Information, Storage & Stability

Molecular Weight	354.41	Formula	C₁₇H₂₂N₈O	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1246560-33-7	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
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
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Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	0.5% methylcellulose 1 0.2% Tween 80 Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	10.000mg/ml (28.22mM)	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.

In vivo Formulation Calculator (Clear solution)

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% DMSO + % + % Tween 80 + % ddH₂O

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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 (Cell-free assay) 2.6 nM PI3Kδ (Cell-free assay) 2.7 nM PI3Kγ (Cell-free assay) 3.0 nM mTOR (Cell-free assay) 3.4 nM PI3Kβ (Cell-free assay) 21 nM
In vitro	VS-5584 (SB2343) is an ATP-competitive inhibitor which selectively inhibits PI3K/mTOR signalling 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 CD44^Hi/CD24^Lo cells in an HMLER immortalised mammary cancer cell line. In SUM159 cells, it effectively eliminates the cancer stem cell side population. A large human cancer cell line panel screen (436 lines) reveals broad antiproliferative sensitivity and that cells harbouring mutations in PI3KCA are generally more sensitive toward VS-5584 treatment. In the FLT3-ITD harbouring 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.
Kinase Assay	In vitro mTOR kinase assays
Kinase Assay	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-labelled 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 tumours, oral dosing of S7016 decreases tumour cancer stem cells and induces tumour regression in taxane-resistant models. In a PTEN^null human prostate PC3 xenograft model, treatment with S7016 leads to significant tumour 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 tumour growth (28% for 3.7 mg/kg and 76% for 11 mg/kg).
References	[1] http://www.verastem.com/attachments/2012_EORTC_PI3K.pdf [2] https://pubmed.ncbi.nlm.nih.gov/23270925/

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

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VS-5584 (SB2343) PI3K inhibitor

Chemical Structure

Molecular Weight: 354.41