WYE-354

Catalog No.S1266 Batch:S126601

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Technical Data

Formula

C24H29N7O5
Molecular Weight 495.53 CAS No. 1062169-56-5
Solubility (25°C)* In vitro DMSO 99 mg/mL (199.78 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
4%DMSO 30%PEG300 5%Tween80 61%ddH2O
5.0mg/ml 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description 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).
Targets
mTOR [1]
5 nM
In vitro WYE-354 also inhibits several PI3Ks at micromolar levels. In HEK293 cells, WYE-354 (0.2 μM–5 μM) effectively inhibits both mTORC1 and mTORC2. WYE-354 (0.3 μM–10 μM) significantly blocks mTOR signaling and Akt activation in U87MG and MDA361 cells. Furthermore, WYE-354 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 WYE-354 is accompanied by G1 cell cycle arrest and caspases activation. [1] In endothelial HUVEC cells, WYE-354 (10 nM–1 μM) also inhibits both mTORC1 and mTORC2 signaling, as revealed by dephosphorylation of S6 ribosomal protein and Akt, respectively. Furthermore, WYE-354 (10 nM–1 μM) activates mitogen-activated protein kinase (MAPK) signaling, which may be due to its inhibition of mTORC1. [2]
In vivo In a mice xenograft model of PTEN-null PC3MM2 tumor, WYE-354 (50 mg/kg) effectively inhibits mTOR signaling and tumor growth. [1]

Protocol (from reference)

Kinase Assay:[1]
  • mTOR inhibitor assays

    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 WYE-354. 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.
Cell Assay:[1]
  • Cell lines

    Tumor cell lines including MDA-MB-361, MDA-MB-231, MDA-MB-468, LNCap, DU145, A498, and HCT116

  • Concentrations

    0–50 μM, dissolved in DMSO

  • Incubation Time

    72 hours

  • Method

    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.
Animal Study:[1]
  • Animal Models

    Nude mice (BALB/c, nu/nu, female) bearing PC3MM2 xenograft

  • Dosages

    50 mg/kg

  • Administration

    Administered via intraperitoneal injection

Customer Product Validation

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

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

, , Dr. Zhang of Tianjin Medical University

Data from [Data independently produced by , , Mol Ther Nucleic Acids, 2018, 11:485-493]

Selleck's WYE-354 has been cited by 13 publications

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
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
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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.