LY2109761

Catalog No.S2704

LY2109761 Chemical Structure

Molecular Weight(MW): 441.52

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

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Cited by 39 Publications

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Biological Activity

Description LY2109761 is a novel selective TGF-β receptor type I/II (TβRI/II) dual inhibitor with Ki of 38 nM and 300 nM in a cell-free assay, respectively; shown to negatively affect the phosphorylation of Smad2.
Targets
TβRI [1]
(Cell-free assay)
TβRII [1]
(Cell-free assay)
38 nM(Ki) 300 nM(Ki)
In vitro

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. [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-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. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HepG2  MmPzSpVv[3Srb36gRZN{[Xl? NHLVRY4yOMLizszNxsA> NEPYe|EzKGh? NYjSbGU5cW6qaXLpeJMh[XW2b4DoZYd6KGmwZIXjeIlwdiCkeTDnZYxidmerbh?= M1rnSlI2OjZ6MES2
PC-3 NVjCXGR2TnWwY4Tpc44hSXO|YYm= MnPENE4zNzJxNDFOwG0> NUXhbXc1OjRiaB?= MoPFSG1UVw>? NWj1WFZIcW6qaXLpeJMhXEeILd8yNgKBm2mwZIXj[YQhW22jZEKgZYN1cX[jdHnvci=> MWqyNlE4OzB3Mx?=
PMOs MX\GeY5kfGmxbjDBd5NigQ>? NFnGfGIxNjJxMj:0JO69VQ>? M1nTOFI1KGh? NGrJXWRFVVOR NEHHXY5qdmirYnn0d{BVT0ZvzsKx5qCUcW6mdXPl[EBUdWGmMjDhZ5RqfmG2aX;u NIPFSGkzOjF5M{C1Ny=>
PC-3 NVPSWHdiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIC3RmYxNjJxMjFOwG0> MnXRNlQhcA>? NHnj[mVFVVOR NX\RSoRu[myxY3vzJJRp\SCrbnjpZol1cW:wIH;mJINmdGxicILvcIln\XKjdHnvckBxem:mdXPl[EBjgSCWR1[t{tIy NUWydGZyOjJzN{OwOVM>
PMOs Mk\zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnPGNE4zNzJizszN M3\MflI1KGh? NUnreXB[TE2VTx?= NFT0NWdjdG:la4OgeIhmKGmwaHnibZRqd25ib3[gZ4VtdCCycn;sbYZmemG2aX;uJJBzd2S3Y3XkJIJ6KFSJRj5OtlE> MVyyNlE4OzB3Mx?=
U87MG MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1;DV|UwOTBizszN MUCyJIg> NFrVZmZmdmijbnPld{Bz[WSrb4PlcpNqfGm4aYT5 MXOyNlAxPjl7OB?=
T98 MlX4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml3pOU8yOCEQvF2= M2XYb|IhcA>? NWnCSo9R\W6qYX7j[ZMhemGmaX;z[Y5{cXSrdnn0fS=> M37MWlIzODB4OUm4
U87MG NW[yVI42SXCxcITvd4l{KEG|c3H5 MX2xNEDPxE1? Mo\XNkBp NH7PbINmdmijbnPld{Bz[WSrYYTpc44ucW6mdXPl[EBFVkFiZHHtZYdmKGGwZDDhdI9xfG:|aYOgdoF1\XN? NVjNRYZ2OjJyME[5PVg>
NMA-23 MV;BdI9xfG:|aYOgRZN{[Xl? NEfoemsyOCEQvF2= NGDPVWUzKGh? MVXlcohidmOnczDyZYRq[XSrb36tbY5lfWOnZDDEUmEh\GGvYXflJIFv\CCjcH;weI9{cXNicnH0[ZM> M{jGdFIzODB4OUm4
HLE  M3XFbGZ2dmO2aX;uJGF{e2G7 MmHPNE4xOS1zMEFCpI5O NGPsV5c1QCCq NFzr[GxqdmirYnn0d{B1cGVibXnndoF1cW:wIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{ NVnuNoR[OjB6NES4O|g>
HLF NVO0[mxsTnWwY4Tpc44hSXO|YYm= NFK1XmoxNjBzLUGwNOKhdk1? MY[0PEBp M{HUd4lvcGmkaYTzJJRp\SCvaXfyZZRqd25iaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XJ? M2D6WlIxQDR2OEe4
10A/HER2YVMA NI[xR|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn\hNE4yNTBwNTFOwG0> MkPtPUBl MlPpdoVlfWOnczD0bIUhe2m8ZTygbY53[XOrdnXu[ZN{KGGwZDDj[YxtKG63bXLldkBw\iClb3zvcolmew>? M{DOWVIxOzh|MUm3
MC38  NWDqemRDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUL0fYNMPSEQvF2= M3;4WVUh\A>? MonhbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTD0bY1mNWSncHXu[IVvfCCvYX7u[ZI> NYDi[JFGOTl7MEm3OFQ>
U937 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVXqfYk6PS1{MDFOwG0> NUTNOGtjOjRvN{KgbC=> NGXXWYRqdmirYnn0d{Bk\WyuIHfyc5d1cCC|bHnnbJRtgQ>? M3TuSFE5PDl{MUGz
HLE  MUDDfZRwfG:6aYT5JGF{e2G7 M{\qN|AvODBzLUKwJO69VQ>? NIDvV2E1QCCq MULpcoR2[2W|IHPlcIwh[3m2b4TvfIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? MnvONVg{OTh2NEO=
HLF Mn;TR5l1d3SxeHn0fUBCe3OjeR?= MXmwMlAxOS1{MDFOwG0> MnL6OFghcA>? NFnuTXJqdmS3Y3XzJINmdGxiY4n0c5RwgGm2eTDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nch?= MX6xPFMyQDR2Mx?=

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-Smad2 / Smad ; 

PubMed: 29416682     


The expression of p-Smad-2 was down regulated by LY2109761 at the dose ranging from 0.1 to 100 μM.

E-cadherin; 

PubMed: 29416682     


The migration-related protein E-cadherin was signifcantly promoted by LY2109761 in a dose dependent manner, ranging from 1 to 100 μM/L.

β-catenin / MMP-9 / MMP-2 / nm23 / uPA / COX-2 ; 

PubMed: 19909744     


Protein lysates from livers of control mice and LY2109761-treated mice were analyzed by western blotting as indicated. β-actin was used as loading control. NS: non-specific band.

CDK2 / CDK4 / Cyclin D1 / p-Rb ; 

PubMed: 19909744     


Protein lysates from livers of control mice and LY2109761-treated mice were analyzed by western blotting as indicated. β-actin was used as loading control. NS: non-specific band.

29416682 19909744
In vivo Administration 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. [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]

Protocol

Cell Research:[1]
+ Expand
  • Cell lines: Colo357FG/GLT, and Colo357L3.6pl/GLT
  • Concentrations: Dissolved in DMSO, final concentrations ~10 μM
  • Incubation Time: 48 hours
  • Method: Cells 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.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: Athymic nude mice with orthotopic implantation of L3.6pl/GLT cells
  • Formulation: Dissolved in the SX-1292 oral vehicle containing 1% sodium carboxymethylcellulose, 0.5% sodium lauryl sulfate, and 0.05% antifoam
  • Dosages: 50 mg/kg
  • Administration: Twice a day p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 2 mg/mL (4.52 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
0.5% CMC+0.25% Tween 80
For best results, use promptly after mixing.
16 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 441.52
Formula

C26H27N5O2

CAS No. 700874-71-1
Storage powder
in solvent
Synonyms N/A

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID