Item no. |
S1266-5000 |
Manufacturer |
Selleckchem
|
CASRN |
1062169-56-5 |
Amount |
5 g |
Category |
|
Type |
Inhibitors |
Specific against |
other |
ECLASS 10.1 |
32160490 |
ECLASS 11.0 |
32160490 |
UNSPSC |
12000000 |
Alias |
1062169-56-5' |
Similar products |
WYE-354 |
Available |
|
Administration |
Administered via intraperitoneal injection |
Animal Models |
Nude mice (BALB/c, nu/nu, female) bearing PC3MM2 xenograft |
Cell lines |
Tumor cell lines including MDA-MB-361, MDA-MB-231, MDA-MB-468, LNCap, DU145, A498, and HCT116 |
Concentrations |
0–50 uM, dissolved in DMSO |
Description |
WYE-354 is a potent, specific and ATP-competitive inhibitor of mTOR with IC50 of 5 nM. |
Dosages |
50 mg/kg |
Formulation |
Dissolved in 5% ethanol, 5% polysorbate 80, 5% PEG-400 |
IC50 |
5 nM, 5 nM, 5 nM, 5 nM, 5 nM, 5 nM |
In vitro |
WYE-354 also inhibits several PI3Ks at micromolar levels. In HEK293 cells, WYE-354 (0.2 uM–5 uM) effectively inhibits both mTORC1 and mTORC2. WYE-354 (0.3 uM–10 uM) 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 uM to 2.3 uM. 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 uM) also inhibits both mTORC1 and mTORC2 signaling, as revealed by dephosphorylation of S6 ribosomal protein and Akt, respectively. Furthermore, WYE-354 (10 nM–1 uM) 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] |
Incubation Time |
72 hours |
Kinase Assay |
mTOR inhibitor assays, The assays are performed in 96-well plates for 2 hours at room temperature in 25 uL containing 6 nM Flag-TOR(3.5), 1 uM His6-S6K, and 100 uM 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 uM) in combination with varying concentrations of WYE-354. The assays contained 12 nM Flag-TOR(3.5), 1 uM His-S6K, and are incubated for 30 min. The assay results are similarly detected by DELFIA and processed for generation of double-reciprocal plots. |
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. |
Molecular Weight (MW) |
495, 53 |
Picture ChemicalStructure Description |
WYE-354 Chemical Structure |
Picture Description 1 |
, , Dr. Yong-Weon Yi from Georgetown University Medical Center, WYE-354purchased from Selleck, For MTT assays, cells (2, 000 ca. 5, 000 cells/well) were subcultured into 96-well plates according to their growth properties. Cell proliferation was assayed at 72 hr after treatment of WYE-354 by adding 20 l of 5 mg/ml 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) solution per 100 l of growth medium. After incubating for 3-4 h at 37C, the media were removed and 150 l/well of MTT solvent (either absolute DMSO or isopropanol containing 4 M HCl and 0.1% Nonidet-40) was added to dissolve the formazan. |
Picture Description 2 |
, , Dr. Pierre P. Roger from Free University of Brussels, WYE-354purchased from Selleck, HCT116 were left untreated (C) or stimulated for 5 h with serum (FBS) and rapamycin or WYE-354 at the indicated concentrations. |
Solubility (25C) |
DMSO 99 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL |
Storage |
2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO |
Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.
All products are intended for research use only (RUO). Not for human, veterinary or therapeutic use.