The mammalian target of rapamycin (mTOR) is centrally involved in cell growth, metabolism, and angiogenesis[3]. WYE-354 is an ATP-competitive mTOR inhibitor with an IC50 of 5 nM. WYE-354 also inhibits PI3Kα and PI3Kγ with IC50s of 1.89 μM and 7.37 μM, respectively [3]. In vitro assays showed WYE-354 significantly reduced cell viability, migration and invasion and phospho-P70S6K expression in GBC cells[4]. When injected into tumor-bearing mice, WYE-354 inhibited mTORC1 and mTORC2 and displayed robust antitumor activity in PTEN-null tumors [3]. Mice harboring subcutaneous gallbladder tumors, treated with WYE-354, exhibited a significant reduction in tumor mass. A short-term treatment with a higher dose of WYE-354 decreased the tumor size by 68.6% and 52.4% , in mice harboring G-415 or TGBC-2TKB tumors, respectively, compared to the control group[4].
WYE-354 细胞实验
Cell Line
Concentration
Treated Time
Description
References
T. brucei brucei
0.58 µM
WYE-354 showed modest activity against T. brucei brucei.
PLoS Negl Trop Dis. 2011 Aug;5(8):e1297.
Leishmania major promastigotes
4.1 µM
WYE-354 showed modest activity against Leishmania major promastigotes.
PLoS Negl Trop Dis. 2011 Aug;5(8):e1297.
MCF7
0.644 μM
72 h
WYE-354 effectively inhibited MCF7 cell proliferation with an IC50 of 0.644 mmol/L.
Acta Pharm Sin B. 2025 Jan;15(1):133-150.
MDA-MB-231
1.908 μM
72 h
WYE-354 effectively inhibited MDA-MB-231 cell proliferation with an IC50 of 1.908 mmol/L.
Acta Pharm Sin B. 2025 Jan;15(1):133-150.
WYE-354 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
TG221 transgenic mice
Oral
10 mg/kg
Daily for 3 weeks
WYE-354 exhibited comparable anti-tumor activity to miR-199a-3p in the TG221 mouse model, indicating the importance of the MTOR pathway in tumor development.
Mol Ther Nucleic Acids. 2018 Jun 1;11:485-493
Nude mice
MDA-MB-231 xenograft model
Intraperitoneal injection
1, 3, 10 mg/kg
Daily for 15 days
WYE-354 significantly inhibited tumor growth in the MDA-MB-231 xenograft model, with tumor weight inhibition rates of 28.3%, 55.4%, and 76.6% and tumor volume inhibition rates of 30.7%, 60.0%, and 79.5% at doses of 1, 3, and 10 mg/kg, respectively.
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