Molecular Formula | C24H29N7O5 |
Molar Mass | 495.53 |
Density | 1.46 |
pKa | 13.42±0.70(Predicted) |
Storage Condition | Sealed in dry,Store in freezer, under -20°C |
In vitro study | In the DELFIA measuring His6-S6K1 T389 phosphorylation, WYE-354 inhibits recombinant mTOR enzyme with an IC 50 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. |
In vivo study | The effect of Rapamycin and WYE-354 on tumor growth is evaluated in xenograft GBC tumor models. 2×10 6 or 5×10 6 cells of G-415 or TGBC2TKB, respectively, are xenotransplanted into NOD-SCID mice subcutaneously. When tumors reach an average volume of 100 mm 3 , 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. |
1mg | 5mg | 10mg | |
---|---|---|---|
1 mM | 2.018 ml | 10.09 ml | 20.18 ml |
5 mM | 0.404 ml | 2.018 ml | 4.036 ml |
10 mM | 0.202 ml | 1.009 ml | 2.018 ml |
5 mM | 0.04 ml | 0.202 ml | 0.404 ml |