ArtNr |
S2704-5 |
Hersteller |
Selleckchem
|
CAS-Nr. |
700874-71-1 |
Menge |
5 mg |
Kategorie |
|
Typ |
Inhibitors |
Specific against |
other |
ECLASS 10.1 |
32160490 |
ECLASS 11.0 |
32160490 |
UNSPSC |
12000000 |
Alias |
TbetaRI, TbetaRII;TGF-beta/Smad |
Similar products |
LY2109761 |
Lieferbar |
|
Administration |
Twice a day p.o. |
Animal Models |
Athymic nude mice with orthotopic implantation of L3.6pl/GLT cells |
Cell lines |
Colo357FG/GLT, and Colo357L3.6pl/GLT |
Chemical Name |
7-(2-morpholinoethoxy)-4-(2-(pyridin-2-yl)-5, 6-dihydro-4H-pyrrolo[1, 2-b]pyrazol-3-yl)quinoline |
Concentrations |
Dissolved in DMSO, final concentrations ca.10 uM |
Description |
LY2109761 is a novel selective TGF-beta receptor type I/II (TbetaRI/II) dual inhibitor with Ki of 38 nM and 300 nM, respectively. |
Dosages |
50 mg/kg |
Formulation |
Dissolved in the SX-1292 oral vehicle containing 1% sodium carboxymethylcellulose, 0.5% sodium lauryl sulfate, and 0.05% antifoam |
IC50 |
38 nM (Ki), 38 nM (Ki), 38 nM (Ki), 38 nM (Ki), 38 nM (Ki), 38 nM (Ki) |
In vitro |
LY2109761 treatment induces a dose-dependent low-anchorage growth inhibition of L3.6pl/GLT cells, leading to ca.33% or 73% inhibition at 2 uM and 20 uM, respectively, which can be strongly enhanced when combined with gemcitabine in combination index value of 0.36581. Blocking TbetaRI/II kinase activity with LY2109761 (5 uM) completely suppresses both the basal and TGF-beta1-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-beta–induced Smad2 phosphorylation. [1] 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. [2] LY2109761 pretreatment enhances radiosensitivity of glioblastoma cells via TGF-beta signaling blockage. LY2109761 (10 uM) reduces the self-renewal and proliferation of GBM-derived cancer stem–like cells (CSLC), which can be significantly enhanced wcombined with radiation. [3] |
In vivo |
Administration of LY2109761 (50 mg/kg) alone or in combination with gemcitabine (25 mg/kg) significantly reduces the tumor volume by ca.70% and ca.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. [1] 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. [3] |
Incubation Time |
48 hours |
Method |
Cells are exposed to increasing doses of LY2109761 (ca.10 uM) 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. |
Molecular Weight (MW) |
441, 52 |
Picture ChemicalStructure Description |
LY2109761 Chemical Structure |
Solubility (25C) |
DMSO <1 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL |
Storage |
2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO |
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