VS-5584 (SB2343)

製品コードS7016 バッチS701601

印刷

化学情報

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	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 この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	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.

* <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)は、強力で選択的なデュアルPI3K/mTOR阻害剤で、mTOR、PI3Kα/β/δ/γに対してそれぞれIC50値が3.4 nMおよび2.6-21 nMです。第1相。
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 CD44^Hi/CD24^Lo cells in an HMLER immortalized 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 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.
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. In a PTEN^null 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).

プロトコル(参考用のみ)

キナーゼアッセイ	In vitro mTOR kinase assays
キナーゼアッセイ	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.
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 was used to evaluate the effect of VS-5584 (SB2343), and this compound was tested for its activity.
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

参考

http://www.verastem.com/attachments/2012_EORTC_PI3K.pdf
https://pubmed.ncbi.nlm.nih.gov/23270925/

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
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
[ ACS Pharmacol Transl Sci, 2019, ]	PubMed: 32259061

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。