WYE-354

製品コードS1266 バッチS126601

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

C₂₄H₂₉N₇O₅

分子量

495.53

CAS No.

1062169-56-5

Solubility (25°C)*

体外

DMSO

99 mg/mL (199.78 mM)

Water

Insoluble

Ethanol

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.
Clear solution	4%DMSO 1 30%PEG300 2 5%Tween80 3 61%ddH2O 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。	5.000mg/ml (10.09mM)	Taking the 1 mL working solution as an example, add 40 μL of 125 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 610 μL of ddH2O to adjust the volume to 1 mL. 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	WYE-354 is a potent, specific and ATP-competitive inhibitor of mTOR with IC50 of 5 nM, blocks mTORC1/P-S6K(T389) and mTORC2/P-AKT(S473) not P-AKT(T308), selective for mTOR than PI3Kα (>100-fold) and PI3Kγ (>500-fold).
in vitro	WYE-354 also inhibits several PI3Ks at micromolar levels. In HEK293 cells, this compound (0.2 μM–5 μM) effectively inhibits both mTORC1 and mTORC2. It (0.3 μM–10 μM) significantly blocks mTOR signaling and Akt activation in U87MG and MDA361 cells. Furthermore, this chemical potently inhibits proliferation in tumor cell lines including MDA-MB-361, MDA-MB-231, MDA-MB-468, LNCap, A498, and HCT116, with IC50 values ranging from 0.28 μM to 2.3 μM. The apoptosis induced by this compound is accompanied by G1 cell cycle arrest and caspases activation. In endothelial HUVEC cells, it (10 nM–1 μM) also inhibits both mTORC1 and mTORC2 signaling, as revealed by dephosphorylation of S6 ribosomal protein and Akt, respectively. Furthermore, this chemical (10 nM–1 μM) activates mitogen-activated protein kinase (MAPK) signaling, which may be due to its inhibition of mTORC1.
in vivo	In a mice xenograft model of PTEN-null PC3MM2 tumor, WYE-354 (50 mg/kg) effectively inhibits mTOR signaling and tumor growth.

プロトコル(参考用のみ)

キナーゼアッセイ	mTOR inhibitor assays
キナーゼアッセイ	The assays are performed in 96-well plates for 2 hours at room temperature in 25 μL containing 6 nM Flag-TOR(3.5), 1 μM His6-S6K, and 100 μM ATP. The assays are performed and detected by DELFIA employing the Eu-phospho-p70S6K T389 antibody. For inhibitor versus ATP matrix competition, mTOR kinase reactions are carried out with varying concentrations of ATP (0, 25, 50 100, 200, 400, and 800 μM) in combination with varying concentrations of this compound. The assays contained 12 nM Flag-TOR(3.5), 1 μM His-S6K, and are incubated for 30 min. The assay results are similarly detected by DELFIA and processed for generation of double-reciprocal plots.
細胞アッセイ	細胞株	Tumor cell lines including MDA-MB-361, MDA-MB-231, MDA-MB-468, LNCap, DU145, A498, and HCT116
	濃度	0–50 μM, dissolved in DMSO
	反応時間	72 hours
	実験の流れ	Cells are plated in 96-well plates at 1000 to 3000 cells per well for 24 hours, treated with DMSO or varying concentrations of WYE-354. Viable cell densities are determined 72 hours later by MTS assay employing a CellTiter 96 kit. The effect of each treatment is calculated as percent of control growth relative to the DMSO-treated cells grown in the same culture plate. Inhibitor dose response curves are plotted for determination of IC50 values.
動物実験	動物モデル	Nude mice (BALB/c, nu/nu, female) bearing PC3MM2 xenograft
	投薬量	50 mg/kg
	投与方法	Administered via intraperitoneal injection

参考

https://pubmed.ncbi.nlm.nih.gov/19584280/
https://pubmed.ncbi.nlm.nih.gov/21439267/

カスタマーフィードバック

: , , Dr. Zhang of Tianjin Medical University

: , , Dr. Yong-Weon Yi from Georgetown University Medical Center

: , , Dr. Pierre P. Roger from Free University of Brussels

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：

A Novel Pipeline for Drug Repurposing for Bladder Cancer Based on Patients' Omics Signatures [ Cancers (Basel), 2020, 12(12)E3519]	PubMed: 33255925
WYE-354 restores Adriamycin sensitivity in multidrug-resistant acute myeloid leukemia cell lines. [ Oncol Rep, 2019, 41(6):3179-3188]	PubMed: 30942458
miR-199a-3p Modulates MTOR and PAK4 Pathways and Inhibits Tumor Growth in a Hepatocellular Carcinoma Transgenic Mouse Model [Callegari E, et al. Mol Ther Nucleic Acids, 2018, 11:485-493]	PubMed: 29858083
Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative breast cancer cells [ Int J Oncol, 2018, 52(3):828-840]	PubMed: 29344641
The Toxmatrix: Chemo-Genomic Profiling Identifies Interactions That Reveal Mechanisms of Toxicity [ Chem Res Toxicol, 2018, 31(2):127-136]	PubMed: 29156121
Autophagy inhibition sensitizes WYE-354-induced anti-colon cancer activity in vitro and in vivo. [Wang L, et al. Tumour Biol, 2016, 37(9):11743-11752]	PubMed: 27020593
β-TrCP1 degradation is a novel action mechanism of PI3K/mTOR inhibitors in triple-negative breast cancer cells. [Yi YW, et al. Exp Mol Med, 2015, 47:e143]	PubMed: 25721419
NFκB up-regulation of glucose transporter 3 is essential for hyperactive mammalian target of rapamycin-induced aerobic glycolysis and tumor growth. [ Cancer Lett, 2015, 359(1):97-106]	PubMed: 25578782
NFκB up-regulation of glucose transporter 3 is essential for hyperactive mammalian target of rapamycin-induced aerobic glycolysis and tumor growth. [Zha X, et al. Cancer Lett, 2015, 359(1):97-106]
mTOR regulates phagosome and entotic vacuole fission. [Krajcovic M, et al. Mol Biol Cell, 2013, 24(23):3736-45]	PubMed: 24088573

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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