VS-5584 (SB2343)

製品コードS7016 バッチS701601

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C17H22N8O
分子量 354.41 CAS No. 1246560-33-7
Solubility (25°C)* 体外 DMSO 71 mg/mL (200.33 mM)
Ethanol 3 mg/mL (8.46 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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]

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 SNU-478, SNU-1196, SNU-245, SNU-1079, SNU-308, and SNU-869
濃度 ~10 μM
反応時間 48 h
実験の流れ CellTiter-Glo assay
動物実験 動物モデル Male (PC3 and COLO 205) or female (MV4-11 and HuH7) BALB/c nude mice or female SCID mice (NCI-N87)
投薬量 11 mg/kg, 25 mg/kg once daily
投与方法 orally

カスタマーフィードバック

, , 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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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