LY2109761

Catalog No.S2704

For research use only.

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. LY2109761 blocks autophagy and induces apoptosis.

LY2109761 Chemical Structure

CAS No. 700874-71-1

Selleck's LY2109761 has been cited by 113 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. LY2109761 blocks autophagy and induces apoptosis.
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  NGXROXBHfW6ldHnvckBCe3OjeR?= MW[xNOKh|ryPwrC= Ml\ONkBp MoLTbY5pcWKrdIOgZZV1d3CqYXf5JIlv\HWldHnvckBjgSCpYXzhcodqdg>? MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJ4OEC0Okc,OjV{NkiwOFY9N2F-
PC-3 MkDSSpVv[3Srb36gRZN{[Xl? M4fnZVAvOi9{L{Sg{txO MXWyOEBp NW\1UHdZTE2VTx?= NGHqNXRqdmirYnn0d{BVT0ZvzsKx5qCUcW6mdXPl[EBUdWGmMjDhZ5RqfmG2aX;u MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF5M{C1N{c,OjJzN{OwOVM9N2F-
PMOs NEO1PYRHfW6ldHnvckBCe3OjeR?= NUXzOYVUOC5{L{KvOEDPxE1? MoDUNlQhcA>? NEfTd5lFVVOR NH\5b|dqdmirYnn0d{BVT0ZvzsKx5qCUcW6mdXPl[EBUdWGmMjDhZ5RqfmG2aX;u M4PETFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MUezNFU{Lz5{MkG3N|A2OzxxYU6=
PC-3 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWewMlIwOiEQvF2= NUi0bIhzOjRiaB?= NFPJfnJFVVOR MUficI9kc3NidHjlJIlvcGmkaYTpc44hd2ZiY3XscEBxem:uaX\ldoF1cW:wIIDyc4R2[2WmIHL5JHRITi4QskG= MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF5M{C1N{c,OjJzN{OwOVM9N2F-
PMOs NFzzN|hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV:wMlIwOiEQvF2= NFLSZ3MzPCCq NFfiOHRFVVOR MonTZoxw[2u|IITo[UBqdmirYnn0bY9vKG:oIHPlcIwheHKxbHnm[ZJifGmxbjDwdo9lfWOnZDDifUBVT0ZvzsKx NX7L[GtWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKxO|MxPTNpPkKyNVc{ODV|PD;hQi=>
U87MG MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnnOOU8yOCEQvF2= M3XKTlIhcA>? NYTrboxI\W6qYX7j[ZMhemGmaX;z[Y5{cXSrdnn0fS=> M4jmWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MEC2PVk5Lz5{MkCwOlk6QDxxYU6=
T98 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4DISlUwOTBizszN M2DHPVIhcA>? NEH6SotmdmijbnPld{Bz[WSrb4PlcpNqfGm4aYT5 NXG5U5Q6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKwNFY6QThpPkKyNFA3QTl6PD;hQi=>
U87MG MYHBdI9xfG:|aYOgRZN{[Xl? NIDJdVEyOCEQvF2= NGjDNpczKGh? M1TZWoVvcGGwY3XzJJJi\GmjdHnvck1qdmS3Y3XkJGRPSSCmYX3h[4Uh[W6mIHHwc5B1d3OrczDyZZRmew>? MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjByNkm5PEc,OjJyME[5PVg9N2F-
NMA-23 NH\6fJJCeG:ydH;zbZMhSXO|YYm= M3viUVExKM7:TR?= NGrHOXkzKGh? NGnyVoFmdmijbnPld{Bz[WSrYYTpc44ucW6mdXPl[EBFVkFiZHHtZYdmKGGwZDDhdI9xfG:|aYOgdoF1\XN? MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjByNkm5PEc,OjJyME[5PVg9N2F-
HLE  NEHyUlBHfW6ldHnvckBCe3OjeR?= MVOwMlAyNTFyMNMgcm0> NX34e3RYPDhiaB?= MYDpcohq[mm2czD0bIUhdWmpcnH0bY9vKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz MmX3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB6NES4O|goRjJyOES0PFc5RC:jPh?=
HLF M1[5TmZ2dmO2aX;uJGF{e2G7 M1nmS|AvODFvMUCwxsBvVQ>? NXnacZdmPDhiaB?= NX;hXZZUcW6qaXLpeJMhfGinIH3p[5JifGmxbjDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nch?= NEPUcXk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEi0OFg4QCd-MkC4OFQ5Pzh:L3G+
10A/HER2YVMA MmnoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUfkOnp3OC5zLUCuOUDPxE1? Ml;3PUBl NF6w[2Nz\WS3Y3XzJJRp\SC|aYrlMEBqdn[jc3n2[Y5me3NiYX7kJINmdGxiboXtZoVzKG:oIHPvcI9vcWW| NUHZUGh3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkCzPFMyQTdpPkKwN|g{OTl5PD;hQi=>
MC38  NIDJeY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnLUOUDPxE1? NYfNNnM6PSCm NG\GZ3BqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJJRqdWVvZHXw[Y5l\W62IH3hco5meg>? NVi4Zmp5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm5NFk4PDRpPkG5PVA6PzR2PD;hQi=>
U937 M1zqS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHPmNFM2NTJyIN88US=> MVGyOE04OiCq NIq2TGZqdmirYnn0d{Bk\WyuIHfyc5d1cCC|bHnnbJRtgQ>? M3PVcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6NEmyNVE{Lz5zOES5NlEyOzxxYU6=
HLE  M4nTd2N6fG:2b4jpeJkhSXO|YYm= NXzZR|F3OC5yMEGtNlAh|ryP NX7kWIpqPDhiaB?= NYLzRno6cW6mdXPld{Bk\WyuIHP5eI91d3irdImgbY4h[SCmb4PlMYRmeGWwZHXueEBu[W6wZYK= MmXvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh|MUi0OFMoRjF6M{G4OFQ{RC:jPh?=
HLF M{jzWmN6fG:2b4jpeJkhSXO|YYm= NGjC[WgxNjByMT2yNEDPxE1? M1;NTlQ5KGh? NEK3PGRqdmS3Y3XzJINmdGxiY4n0c5RwgGm2eTDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nch?= MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDNzOES0N{c,OTh|MUi0OFM9N2F-
Sf9 NXqxSXpYTnWwY4Tpc44h[XO|YYm= M4HkRlEhcHJ? MXfJcohq[mm2aX;uJI9nKGi3bXHuJGhqey22YXfn[YQhXEeIYnX0ZXIyKFR{METEJI12fGGwdDDlfJBz\XO|ZXSgbY4hW2Z7IHnud4VkfCClZXzsd{Bi\nSncjCxJIhzKGK7IFjUVmYh[XO|YYmsJGlEPTBiPTCwMlAxOzdizszNMi=> NYfxZ201RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0NlI{OzJpPkK5OFIzOzN{PD;hQi=>
Sf9 MYXGeY5kfGmxbjDhd5NigQ>? MmfBTY5pcWKrdHnvckBw\iCWR1\i[ZRiKHS7cHWgdoVk\XC2b4KgNUBCVEt3IDjUNlA1TCliZYjwdoV{e2WmIHnuJHNnQSClZXzsd{whUUN3MDC9JFAvODZ7IN88UU4> MmPEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTh|MUS5OFMoRjF6M{G0PVQ{RC:jPh?=
Mv1Lu-p3TP-Lux M4rVOGFvfGmycn;sbYZmemG2aY\lJIF{e2G7 M2TRRmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgcYlvcyCPdkHMeU1xO1SSLVz1fEBk\WyuczDifUBtfWOrZnXyZZNmKHKncH;yeIVzKGG|c3H5MEBKSzVyIE2gNE4yQCEQvF2u NXfPb5ZYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUizNVQ6PDNpPkG4N|E1QTR|PD;hQi=>
NIH3T3 M3TtV2FvfGmycn;sbYZmemG2aY\lJIF{e2G7 MnP1RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDtc5V{\SCQSVizWFMh[2WubIOgZpkhYzOKXYTofY1q\GmwZTDhd5NigSxiSVO1NEA:KDBwMkGg{txONg>? M{LPUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6M{G0PVQ{Lz5zOEOxOFk1OzxxYU6=
Calu6 NXL3SotYTnWwY4Tpc44h[XO|YYm= NYqxSoNYUW6qaXLpeIlwdiCxZjDUS2Zj\XSjIIT5dIUhemWlZYD0c5IhOSCrbjDvdoFtdHliZH;z[YQhcHWvYX6gR4FtfTZiY3XscJMhgGWwb3fyZYZ1\WRibX;1d4Uh[nliSW\UTUBxcGG{bXHjc4tqdmW2aXOgZZN{[XluIFXDOVAhRSByLkKzOkDPxE1w MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDNzNEm0N{c,OTh|MUS5OFM9N2F-
T-cells MlfRSpVv[3Srb36gZZN{[Xl? Mn\xNUBpeg>? MYDJcohq[mm2aX;uJI9nKFSJRnLleIFTOSCrbjDoeY1idiCycnntZZJ6KFRvY3XscJMh[XO|ZYPz[YQh[XNiVFfGZoV1[S2|dHnteYxifGWmIGDTUWFFKHCqb4PwbI9zgWyjdHnvckBxemWrbnP1ZoF1\WRiZn;yJFEhcHJiZn;scI94\WRiYomgWGdH[mW2YTDh[IRqfGmxbjDt[YF{fXKnZDDh[pRmeiB7MDDtbY5{KGK7IFHsdIhiKHOlcnXlckBie3OjeTygTWM2OCB;IECuN|ch|ryPLh?= NIrUXFM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSyNlM{Oid-Mkm0NlI{OzJ:L3G+
Mv1Lu M{G4T2Z2dmO2aX;uJIF{e2G7 NV\P[GRWOSCqch?= NXm5SXh5UW6qaXLpeIlwdiCxZjDUS2Zj\XSjUkGgbY4hdWmwazDNelFNfSClZXzsd{Bie3Onc4Pl[EBieyCWR1\i[ZRiNXO2aX31cIF1\WRiUGPNRWQzKHCqb4PwbI9zgWyjdHnvckBxemWrbnP1ZoF1\WRiZn;yJFEhcHJiZn;scI94\WRiYomgWGdH[mW2YTDh[IRqfGmxbjDt[YF{fXKnZDDh[pRmeiBzNTDtbY5{NCCLQ{WwJF0hOC55NTFOwG0v NWTjW215RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0NlI{OzJpPkK5OFIzOzN{PD;hQi=>
Assay
Methods Test Index PMID
Western blot CDK2 / CDK4 / Cyclin D1 / p-Rb ; β-catenin / MMP-9 / MMP-2 / nm23 / uPA / COX-2 ; E-cadherin ; p-Smad2 / Smad 19909744 29416682
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 (from reference)

Cell Research:[1]
  • 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.
Animal Research:[1]
  • Animal Models: Athymic nude mice with orthotopic implantation of L3.6pl/GLT cells
  • Dosages: 50 mg/kg
  • Administration: Twice a day p.o.

Solubility (25°C)

In vitro

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 (suspensions)
For best results, use promptly after mixing.

16 mg/mL

Chemical Information

Molecular Weight 441.52
Formula

C26H27N5O2

CAS No. 700874-71-1
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1CC2=C(C(=NN2C1)C3=CC=CC=N3)C4=C5C=CC(=CC5=NC=C4)OCCN6CCOCC6

In vivo Formulation Calculator (Clear solution)

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%DMSO %

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Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
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Molarity Calculator

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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