The TGF-β pathway regulates a wide variety of cellular processes in many different cell types and biological contexts. There are three identified TGF receptor ligands, TGF-β1, 2 and 3. Activated TGF-β ligands can interact with TGF-β type II receptors (TβRII), then recruit and phosphorylate the TGF-β type I receptors (also called as TβRI or ALK5). In turn, activated TβRI phosphorylates SMAD2 and SMAD3 at C-terminal serine residues. Following that, phosphorylated SMAD and SMAD3 assemble into heterodimeric and trimeric complexes with SMAD4. Then the trimeric complex translocates into the nucleus and regulates the expression of TGF-β target genes[2]. LY364947 is a multiple inhibitor with IC50 values of 0.059, 0.4, 1.4uM for TGF-βRI, TGF-βRII and MLK-7, respectively (measured by kinase activity)[1]. Addition of 400nM LY364947 for 24h can block the Smad phosphorylation induced by exogenous TGFβ1 in U251, U87MG and GL261 glioma cell lines. Pre-treatment with 400nM LY364947 for24 hours before radiation exposure could significantly increase the radio sensitivity in all the three cell lines, accompanied with the decreased radiation-induced phosphorylation of ATM Ser-1981 and P53-Ser15 as well as fewer γH2AX foci, a marker of DNA damage response. These indicated that TGFβ inhibition by LY364947 could abrogate the response to DNA damage and increase radio sensitivity in glioma cells[3]. Treatment with 2µM LY364947 for 24h can prevent TGF-β-induced epithelial-mesenchymal transition in NMuMg cells[4].
作用机制
LY364947 is an ATP competitive inhibitor of the TGFβ type I receptor.[4]
LY364947 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
HepG2 cells
Function assay
Inhibition of TGF-beta-induced expression of PAI-luciferase reporter in HepG2 cells, IC50=0.06 μM
14643325
mink Mv1Lu lung cells
Function assay
Inhibition of TGFbeta R1 induced transcriptional activation of p3TP-Lux in mink Mv1Lu lung cells, IC50=0.04 μM
16539403
NIH3T3 cells
Function assay
Inhibitory activity against TGF-beta-stimulated proliferation in NIH3T3 cells, IC50=0.081 μM
16539403
Sf9 cells
Function assay
Inhibition of human Transforming growth factor (TGF) beta-1 receptor (T204D mutation) autophosphorylation in Sf9 cells, IC50=0.051 μM
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