The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that integrates with multiple pathways involving cell growth, survival and cancer physiology. OSI-027 is an ATP-competitive inhibitor of mTOR kinase with an IC50 value of 4 nM. OSI-027 targeted both mTORC1 and mTORC2 , the two complexes of mTOR, with IC50 values of 22 and 65 nM, respectively. In mechanistic cell assay, OSI-027 inhibited mTOR signaling of phospho-4E-BP1 with an IC50 value of 1 μM. Treatment with OSI-027 (0.001 - 10 μΜ) dose-dependently suppressed Akt phosphorylation and the downstream substrate of Akt, PRAS40, in ovcar-3 ovarian carcinoma cells[3]. In acute myeloid leukemia (AML) cells, OSI-027 blocked mTORC1 and mTORC2 activities at the concentration of 10 μΜ. The incubation with 10 μΜ OSI-027 also suppressed the mRNA translation of cyclin D1 and other proliferation-related genes in AML cells[4]. In GEO colorectal xenograft mice, administration of OSI-027 (65 mg/kg) for 12 days inhibited both mTORC1 and mTORC2 effectors, and slowed the tumor growth as compared to the control group[3].
作用机制
OSI-027 is a ATP-competitive inhibitor of mTOR kinase.
OSI-027 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
human Caki1 cells
Cytotoxicity assay
72 h
Cytotoxicity against human Caki1 cells after 72 hrs by MTT assay, IC50=1.9 μM
24445311
human COLO205 cells
Cytotoxicity assay
72 h
Cytotoxicity against human COLO205 cells after 72 hrs by MTT assay, IC50=5.8 μM
24445311
human COLO205 cells
Cytotoxicity assay
72 h
Cytotoxicity against human COLO205 cells after 72 hrs by MTT assay
24836070
human ColoR cells
Cytotoxicity assay
72 h
Cytotoxicity against human ColoR cells after 72 hrs by MTT assay, IC50=5.8 μM
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