Galunisertib (LY2157299)

Orally

4-(2-(6-methylpyridin-2-yl)-5, 6-dihydro-4H-pyrrolo[1, 2-b]pyrazol-3-yl)quinoline-6-carboxamide

LY2157299 is a potent TGFbeta receptor I (TbetaRI) inhibitor with IC50, of 56 nM.

Dissolved in DMSO and diluted in saline

LY2157299 potently inhibits the TGFbeta receptor signaling. LY2157299 abolishes the TGFbeta induced Smad2 phosphorylation in HUVEC cells. LY2157299 also shows dose dependent potentiation of VEGF or bFGF induced cell proliferation in HUVEC. LY2157299 also promotes VEGF induced HUVEC cell migration. LY2157299 potentiates angiogenesis in the in vitro VEGF-stimulated cord formation assay. [2] LY2157299 inhibits TGF-beta–mediated SMAD2 activation and hematopoietic suppression in primary hematopoietic stem cells in a dose-dependent manner. LY2157199 treatment stimulates hematopoiesis from primary MDS bone marrow specimens. [3] In human glioblastoma (GBM) cells, LY2157299 treatment blocks signaling through the heteromeric TGFbeta receptor complex to reduce levels of active, phosphorylated SMAD. [4]

TGF-beta Type I (RIT204D) Receptors reaction, Reactions: 170-200 nM enzyme in 1 x KB (50 mM Tris pH 7.5, 150 mM NaCl, 4 mM MgCl2, 1 mM NaF, 2 mM beta-mercaptoethanol), LY2157299 dilution series in 1 x KB /16% DMSO (20 uM to 1 nM final concentration with 4% DMSO final concentration), reactions are started by adding ATP mix (4 uM ATP/ 1 uCi 33P-alpha-ATP final concentrations) in 1 x KB. Reactions are incubated at 30 C for 1 hour. Reactions are stopped and quantitated using standard TCA/BSA precipitation onto Millipore FB glass fiber filter plates and by liquid scintillation counting on a MicroBeta JET.

LY2157299 Chemical Structure

2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO