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LY2109761
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
LY2109761图片
CAS NO:700874-71-1
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)441.52
FormulaC26H27N5O2
CAS No.700874-71-1
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 2 mg/mL (4.5 mM)
Water: <1 mg/mL
Ethanol:<1 mg/mL
Solubility (In vivo)0.5% CMC+0.25% Tween 80: 16 mg/mL
SynonymsLY2109761; LY 2109761; LY-2109761
实验参考方法
In Vitro

In vitro activity: LY2109761 treatment induces a dose-dependent low-anchorage growth inhibition of L3.6pl/GLT cells, leading to ~33% or 73% inhibition at 2 μM and 20 μM, respectively, which can be strongly enhanced when combined with gemcitabine in combination index value of 0.36581. Blocking TβRI/II kinase activity with LY2109761 (5 μM) completely suppresses both the basal and TGF-β1-stimulated migration and invasion of L3.6pl/GLT cells, significantly enhances the detachment-induced apoptosis by 26% at 8 hours treatment, and completely suppresses TGF-β–induced Smad2 phosphorylation. LY2109761 treatment at 1 nM is sufficient to significantly block the migration and invasion but not adhesion of hepatocellular carcinoma cells by increasing E-cadherin expression. LY2109761 pretreatment enhances radiosensitivity of glioblastoma cells via TGF-β signaling blockage. LY2109761 (10 μM) reduces the self-renewal and proliferation of GBM-derived cancer stem–like cells (CSLC), which can be significantly enhanced when combined with radiation.


Kinase Assay: LY2109761 is an orally active, selective TGF-β receptor type I/II inhibitor with Kis of 38 nM and 300 nM, respectively.


Cell Assay: Cells (Colo357FG/GLT, and Colo357L3.6pl/GLT) are exposed to increasing doses of LY2109761 (~10 μM) for 48 hours. The medium containing drugs is removed, the cells are washed twice with PBS, and fresh medium is added. After 5 days of incubation, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay is used to obtain relative variable cell numbers.

In VivoAdministration of LY2109761 (50 mg/kg) alone or in combination with gemcitabine (25 mg/kg) significantly reduces the tumor volume by ~70% and ~90%, respectively, prolongs the survival with the median survival duration of 45.0 days and 77.5 days, respectively, and reduces spontaneous abdominal metastases in the L3.6pl/GLT Xenograft mice model. In consistent with the in vitro effect, administration of LY2109761 alone or in combination with radiation, markedly inhibits tumor growth in the orthotopical CSLC glioblastoma model by 43.4% and 76.3%, respectively, decreases tumor invasion and tumor microvessel density, and significantly enhances radiation-induced tumor growth delay in the U87MG xenograft mice model.
Animal modelAthymic nude mice with orthotopic implantation of L3.6pl/GLT cells
Formulation & DosageDissolved in the SX-1292 oral vehicle containing 1% sodium carboxymethylcellulose, 0.5% sodium lauryl sulfate, and 0.05% antifoam; 50mg/kg; oral gavage
ReferencesMol Cancer Ther. 2008 Apr;7(4):829-40; Hepatology. 2008 May;47(5):1557-66.