Preclinical evaluation of WYE-687, a mTOR kinase inhibitor, as a potential anti-acute myeloid leukemia agent

Concurrent inhibition of mTORC1 and mTORC2 by WYE-687 inhibits renal cell carcinoma cell growth in vitro and in vivo

“…Since WYE-687 is a novel mTOR kinase inhibitor[20,24], its effect on mTOR signaling was tested. As shown in Fig 4A, treatment with WYE-687 (100 nM, 2 hours) in 786-ORCC cells almost completely blocked phosphorylation (“p-”) of Akt (Ser-473), S6K1 (Thr-389) and S6 (Ser-235/236).…”

“…Within three weeks, the xenograft RCC tumors were established with the average tumor volumes of 100 mm 3 . Half of the mice were treated with WYE-687 (25 mg/kg body weight, oral gavage, daily, for 15 days)[20,24]. The other half mice were administrated with vehicle control (5% ethanol, 2% Tween 80, and 5% polyethylene glycol-400) [24].…”

“…Half of the mice were treated with WYE-687 (25 mg/kg body weight, oral gavage, daily, for 15 days)[20,24]. The other half mice were administrated with vehicle control (5% ethanol, 2% Tween 80, and 5% polyethylene glycol-400) [24]. As demonstrated in Fig 5A, 786-O tumor growth in the WYE-687-administrated mice was significantly slower than that of vehicle control mice.…”

“…Cells were treated with applied WYE-687 in the presence of thymidine (1 μCi/mL, Sigma). Afterwards, cells were washed, and the cellular DNA was precipitated [24]. The aliquots were counted by liquid-scintillation spectrometry.…”

“…Within three week, the tumor xenografts were established, and the tumor volumes were around 100 mm 3 . Mice (n = 10 each group) were treated once daily by gavage with either vehicle control or WYE-687 (25 mg/kg body weight) for 15 consecutive days[20,24]. Mice body weight and bi-dimensional tumor measurements were taken every 5 days.…”