LY2109761

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Chemical Structure| 700874-71-1 同义名 : -
CAS号 : 700874-71-1
货号 : A225920
分子式 : C26H27N5O2
纯度 : 99%+
分子量 : 441.525
MDL号 : MFCD12923354
存储条件：

Pure form Sealed in dry,Store in freezer, under -20°C

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

DMSO: 5 mg/mL(11.32 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+water 0.5 mg/mL clear

PO 0.5% CMC-Na 41 mg/mL suspension

生物活性
靶点

  • TGFβRII

    TβRII, Ki:300 nM

  • TGFβRI/ALK5

    TβRI, Ki:38 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]. LY2109761 is a dual inhibitor of TGF-βRI and TGF-βRII with Ki values of 38 and 300nM (measured by in vitro kinase assay). Pre-treatment with LY2109761 of 5uM concentration for 24h (serum free) can abolish the p-smad2 induced by TGF-β receptor which activated by TGF-β/serum in the following 30min in L3.6pl/GLT cells. Inhibition of TGF-βRI/II pathway with LY2109761 (5uM) significantly enhanced the anoikis in L3.6pl/GLT cells for 8h. LY2109761 of 5uM for 48-hour treatment can abolish the TGF-β1–stimulated migration and invasiveness of L3.6pl/GLT cells, the metastatic variant of pancreatic cancer cells. 50mg/kg of LY2109761 orally given to mice twice a day, 5 days per week for 4 weeks, shows antimetastatic effect in pancreatic cancer cell spontaneous metastasis models[1]. The invasiveness of the embryonic chicken vasculature by HLE tumors were decreased with treatment of 0.1uM LY2109761 for 48h, showing that LY2109761 can inhibit HLE tumors invading stroma and blood vessels[3].
作用机制 LY2109761 binds to the ATP binding site of the TGF-β R1 kinase domain. [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
10A/HER2YVMA 0.1-0.5 μM Growth Inhibition Assay 9 d reduces the size, invasiveness and cell number of colonies 20383197
HepG2 10 μM  Function Assay 2 h inhibits autophagy induction by galangin 25268046
HLE 0.01-100 nM Function Assay 48 h inhibits the migration in a dose-dependent manner 20844878
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.26mL

0.45mL

0.23mL

11.32mL

2.26mL

1.13mL

22.65mL

4.53mL

2.26mL
参考文献

[1]Melisi D, Ishiyama S, et al. LY2109761, a novel transforming growth factor beta receptor type I and type II dual inhibitor, as a therapeutic approach to suppressing pancreatic cancer metastasis. Mol Cancer Ther. 2008 Apr;7(4):829-40.

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

[3]Fransvea E, Mazzocca A, et al. Targeting transforming growth factor (TGF)-betaRI inhibits activation of beta1 integrin and blocks vascular invasion in hepatocellular carcinoma. Hepatology. 2009 Mar;49(3):839-50.

[4]Li HY, McMillen WT, et al. Optimization of a dihydropyrrolopyrazole series of transforming growth factor-beta type I receptor kinase domain inhibitors: discovery of an orally bioavailable transforming growth factor-beta receptor type I inhibitor as antitumor agent. J Med Chem. 2008 Apr 10;51(7):2302-6.