The signal transducer and activator of transcription (STAT) proteins mediate cytokine and growth factor responses, including promoting cell growth and differentiation, and immune responses[1]. STAT3 is a central transcription factor that is activated by phosphorylation of a conserved tyrosine residue (Tyr705) in response to extracellular cytokines and growth factors and is an attractive target for anticancer drug discovery[2]. SH5-07 is an inhibitor of STAT3 with IC50 of 3.9 ± 0.6 μM[3]. 72-h treatment with SH5-07 of cultured tumor cells harboring variable Stat3 activities inhibited viability to different degrees, with IC50 of 1.0-2.7 μM for glioma U251MG and U87MG cells (most sensitive), 3.8-4.5 μM for breast cancer, MDA-MB-231 (231) cells, 3.8-7.4 μM for glioma, U373MG and SF295 cells, 5.3-5.8 μM for DU145 prostate cancer cells, 4.1-9.2 μM for NIH3T3/v-Src (vSrc), and 9.6-10.3 μM for the least sensitive human pancreatic cancer, Panc-1 cells[3]. Tail vein injection of SH5-07 (5-6 mg/kg every 2-3 days) inhibited growth of 90-150 mm3 established subcutaneous mouse xenografts of human glioma (U251MG) and breast (MDA-MB-231) tumors that harbor aberrantly-active Stat3, with decreased c-Myc, Mcl-1 and Cyclin D1 expression. No significant changes in body weights, blood cell counts, or the gross anatomy of organs, or obvious signs of toxicity were observed[3].
作用机制
SH5-07 blocks STAT3 DNA binding activity.
SH5-07 细胞研究
细胞系
浓度
检测类型
检测时间
活性说明
数据源
127EF cells
Cytotoxicity assay
Cytotoxicity against human 127EF cells assessed as cell viability after 3 days by Alamar Blue assay, IC50=0.1955 μM
24900612
147EF cells
Function assay
2 to 72 hrs
Inhibition of STAT3 in human 147EF cells assessed as reduction of phosphorylated Bcl-xL level after 2 to 72 hrs by Western blotting analysis
24900612
25EF cells
Cytotoxicity assay
Cytotoxicity against human 25EF cells assessed as cell viability after 3 days by Alamar Blue assay, IC50=1.1205 μM
24900612
30M cells
Cytotoxicity assay
Cytotoxicity against human 30M cells assessed as cell viability after 3 days by Alamar Blue assay, IC50=0.1 μM
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