General description
A cell-permeable pyrazolopyrimidine compound that acts as a potent and ATP-competitive mTOR inhibitor (IC50 = 5 nM with S6K as the substrate and 100 µM ATP) with much reduced activity against PI 3-Kα or PI 3-Kγ (IC50 = 1.89 and 7.37 µM, respectively) and little or no activity toward 24 other kinases (IC50 >50 µM). WYE-354 is equally potent against mTORC1 and mTORC2 activities in HEK293 immune complex kinase assays using S6K and Akt as the respective substrate (IC50<200 nM; [ATP] = 100 µM) and effectively blocks cellular phosphorylation of S6K on T389 and Akt on S473 both in cultures and in a murine xenograft model, resulting in a significant suppression of PC3MM2-derived tumor growth (by 86% on day 7; 50 mg/kg, i.p twice per day) in vivo.
Packaging
Packaged under inert gas
Preparation Note
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Other Notes
Yu, K., et al. 2009. Cancer Res.69, 6232.
Zask, A., et al. 2009. J. Med. Chem.52, 5013.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)
| Quality Segment | 100 |
| assay | ≥98% (HPLC) |
| form | solid |
| manufacturer/tradename | Calbiochem® |
| storage condition | OK to freeze,protect from light |
| color | white |
| solubility | DMSO: 50 mg/mL |
| shipped in | ambient |
| storage temp. | −20°C |
| SMILES string | N5(CCOCC5)c1nc(nc3c1C=[N]#[N]3C4CCN(CC4)C(=O)OC)c2ccc(cc2)NC(=O)OC |
| InChI | 1S/C24H29N7O5/c1-34-23(32)26-17-5-3-16(4-6-17)20-27-21(29-11-13-36-14-12-29)19-15-25-31(22(19)28-20)18-7-9-30(10-8-18)24(33)35-2/h3-6,15,18H,7-14H2,1-2H3,(H,26,32) |
| InChI key | IMXHGCRIEAKIBU-UHFFFAOYSA-N |
