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CAS No.: 700874-71-1

LY2109761 Catalog No. CSN13478

Synonyms: LY2109761

LY2109761 is a selective TGF-β receptor type I/II (TβRI/II) dual inhibitor with Ki of 38 nM and 300 nM, respectively and is shown to negatively affect the phosphorylation of Smad2.

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400-920-2911

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纯度 & 质量文件批次:

靶点选择性

生物活性

实验方案

技术信息

生物活性

靶点 TGFβR1

Ki:38nM TGFβR2

Ki:300nM
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

Cell Data

Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
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

更多
动物研究
剂量
Mice: 50 mg/kg - 100 mg/kg^[5] (p.o.)

给药途径
p.o.
参考文献

动物研究
剂量	Mice: 50 mg/kg - 100 mg/kg^[5] (p.o.)
给药途径	p.o.

[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.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.2649 mL
- 11.3244 mL
- 22.6488 mL
- 5 mM
- 0.4530 mL
- 2.2649 mL
- 4.5298 mL
- 10 mM
- 0.2265 mL
- 1.1324 mL
- 2.2649 mL

技术信息

CAS号

700874-71-1

储存条件

粉末: Sealed in dry,Store in freezer, under -20°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C26H27N5O2

运输

蓝冰

分子量

441.52

别名

LY2109761

溶解度

DMSO	25.0 mg/mL (56.6 mM) warming
Water	insoluble

动物实验配方

IP	2% DMSO+water	0.5 mg/mL	clear
PO	0.5% CMC-Na	41 mg/mL	suspension

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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
HLE	0.001-20 μM	Cytotoxity Assay	48 h	induces cell cytotoxity in a dose-dependent manner	18318443
HLF	0.01-100 nM	Function Assay	48 h	inhibits the migration in a dose-dependent manner	20844878
HLF	0.001-20 μM	Cytotoxity Assay	48 h	induces cell cytotoxity in a dose-dependent manner	18318443
MC38	5 μM	Growth Inhibition Assay	5 d	inhibits cell growth in a time-dependent manner	19909744
NMA-23	10 μM	Apoptosis Assay	2 h	enhances radiation-induced DNA damage and apoptosis rates	22006998
PC-3	0.2/2/4 μM	Function Assay	24 h	inhibits TGF-β1–induced Smad2 activation	22173053
PC-3	0.2/2 μM	Growth Inhibition Assay	24 h	blocks the inhibition of cell proliferation produced by TGF-β1	22173053
PMOs	0.2/2/4 μM	Function Assay	24 h	inhibits TGF-β1–induced Smad2 activation	22173053
PMOs	0.2/2 μM	Growth Inhibition Assay	24 h	blocks the inhibition of cell proliferation produced by TGF-β1	22173053
T98	5/10 μM	Growth Inhibition Assay	2 h	enhances radiosensitivity	22006998
U87MG	5/10 μM	Growth Inhibition Assay	2 h	enhances radiosensitivity	22006998
U87MG	10 μM	Apoptosis Assay	2 h	enhances radiation-induced DNA damage and apoptosis rates	22006998
U937	5-20 μM	Growth Inhibition Assay	24-72 h	inhibits cell growth slightly	18492113

靶点	Description	IC50
TGFβR1		Ki:38nM
TGFβR2		Ki:300nM

LY2109761 Catalog No. CSN13478

靶点选择性

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