LY2109761

Athymic nude mice with orthotopic implantation of L3.6pl/GLT cells

7-(2-morpholinoethoxy)-4-(2-(pyridin-2-yl)-5, 6-dihydro-4H-pyrrolo[1, 2-b]pyrazol-3-yl)quinoline

LY2109761 is a novel selective TGF-beta receptor type I/II (TbetaRI/II) dual inhibitor with Ki of 38 nM and 300 nM, respectively.

Dissolved in the SX-1292 oral vehicle containing 1% sodium carboxymethylcellulose, 0.5% sodium lauryl sulfate, and 0.05% antifoam

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]

48 hours

441, 52

DMSO <1 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL