LY364947

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Chemical Structure| 396129-53-6 同义名 : -
CAS号 : 396129-53-6
货号 : A131713
分子式 : C17H12N4
纯度 : 98%
分子量 : 272.304
MDL号 : -
存储条件：

Pure form Keep in dark place,Inert atmosphere,Room temperature

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 15 mg/mL(55.09 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 1 mg/mL clear

PO 0.5% CMC-Na 41 mg/mL suspension

生物活性
靶点

  • CK1

    CK1δ, IC50:0.22 μM

  • TGFβRII

    TGFβRII, IC50:0.4 μM

  • TGFβRI/ALK5

    TGFβRI, IC50:59 nM
描述 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]
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
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.67mL

0.73mL

0.37mL

18.36mL

3.67mL

1.84mL

36.72mL

7.34mL

3.67mL
参考文献

[1]Li HY, Wang Y, et al. Dihydropyrrolopyrazole transforming growth factor-beta type I receptor kinase domain inhibitors: a novel benzimidazole series with selectivity versus transforming growth factor-beta type II receptor kinase and mixed lineage kinase-7. J Med Chem. 2006 Mar 23;49(6):2138-42.

[2]Colak S, Ten Dijke P, et al. Targeting TGF-β Signaling in Cancer. Trends Cancer. 2017 Jan;3(1):56-71.

[3]Hardee ME, Marciscano AE, et al. Resistance of glioblastoma-initiating cells to radiation mediated by the tumor microenvironment can be abolished by inhibiting transforming growth factor-β. Cancer Res. 2012 Aug 15;72(16):4119-29.

[4]Peng SB, Yan L, et al. Kinetic characterization of novel pyrazole TGF-beta receptor I kinase inhibitors and their blockade of the epithelial-mesenchymal transition. Biochemistry. 2005 Feb 22;44(7):2293-304.