WYE-354

SKU: orb1227050

Description

WYE-354 is a potent, selective and ATP-competitive inhibitor of mTOR with IC50 of 5 nM (recombinant mTOR ), displays >100-fold selectivity over PI3K isofoms; acutely blocks substrate phosphorylation by mTORC1 and mTORC2 in vitro and in cells in response to growth factor, amino acids, and hyperactive PI3K/AKT, reduces AKT downstream function and inhibits proliferation of diverse cancer cell lines; inhibits mTORC1 and mTORC2 and displayed robust antitumor activity in PTEN-null tumors.

Key Properties

• CAS Number: 1062169-56-5
• MW: 495.5309
• Purity: >98% (HPLC)
• Formula: C₂₄H₂₉N₇O₅
• SMILES: O=C(N1CCC(N2N=CC3=C(N4CCOCC4)N=C(C5=CC=C(NC(OC)=O)C=C5)N=C32)CC1)OC
• Target: mTOR
• Solubility: DMSO: ≥ 26 mg/mL

Bioactivity

• In Vivo:
  The effect of Rapamycin and WYE-354 on tumor growth is evaluated in xenograft GBC tumor models. 2×106 or 5×106 cells of G-415 or TGBC2TKB, respectively, are xenotransplanted into NOD-SCID mice subcutaneously. When tumors reach an average volume of 100 mm3, the mice are treated either with Rapamycin or WYE354. Rapamycin is administered i.p. at a concentration of 10 mg/kg, daily for 5 days per week for 3 weeks, while WYE-354 is administrated at a daily i.p. dose of 50 mg/kg for 5 days. Mice are sacrificed 30 days after the initiation of the treatments and an autopsy is performed that include removal of the entire tumor area. Mice treated with WYE-354 exhibit 68.6% and 52.4% reduction in average tumor size (P<0.01; P<0.01), as well as 82.9% and 45.5% (P<0.01; ns) reduction in tumor weight, respectively.
• In Vitro:
  In the DELFIA measuring His6-S6K1 T389 phosphorylation, WYE-354 inhibits recombinant mTOR enzyme with an IC50 of 5 nM. Cell viability is analyzed by MTS assay. G-415 and TGBC-2TKB cell lines are treated with increasing concentrations of WYE-354 (0.1, 1, 5 and 10 μM) for 24, 48, and 72 hours. WYE-354 significantly reduces cell viability starting at a 1 μM concentration after a 24 hours exposure, in both studied cell lines (P<0.001). A decrease in cell viability is not observed at a dose of 100 nM, except for the TGBC-2TKB cell line after 72 hours of treatment.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

WYE 354 | WYE354

Quick Database Links

Gene Symbol

mTOR