LY2109761 化学構造
分子量: 441.52

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製品説明

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製品の説明

生物活性

製品説明 LY2109761は、新しい選抜TGFβレセプター・タイプIとタイプII(TβRI/II)二重阻害剤で、 Ki がそれぞれ38 nM と 300 nMになる。
ターゲット TβRI TβRII
IC50 38 nM (Ki) 300 nM (Ki) [1]
In vitro試験 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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
HepG2  MXTGeY5kfGmxbjDBd5NigQ>? M334VFExyqEQvF5CpC=> M{TTS|IhcA>? NFu0XlNqdmirYnn0d{BifXSxcHjh[5khcW6mdXP0bY9vKGK7IHfhcIFv\2mw M{HrU|I2OjZ6MES2
PC-3 M2XTS2Z2dmO2aX;uJGF{e2G7 NFPObIExNjJxMj:0JO69VQ>? MlHZNlQhcA>? MkXGSG1UVw>? M1XP[olvcGmkaYTzJHRITi4QskJihLNqdmS3Y3XkJHNu[WR{IHHjeIl3[XSrb36= NE[yPFAzOjF5M{C1Ny=>
PMOs M13OSGZ2dmO2aX;uJGF{e2G7 MUOwMlIwOi92IN88US=> NGDBN5QzPCCq MoD6SG1UVw>? MYHpcohq[mm2czDUS2Yu|rJz4pETbY5lfWOnZDDTcYFlOiCjY4TpeoF1cW:w M1z4NlIzOTd|MEWz
PC-3 MnfjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXHDN3BHOC5{L{Kg{txO M1H1RVI1KGh? NGX0NIdFVVOR MoDlZoxw[2u|IITo[UBqdmirYnn0bY9vKG:oIHPlcIwheHKxbHnm[ZJifGmxbjDwdo9lfWOnZDDifUBVT0ZvzsKx NI\Dcm8zOjF5M{C1Ny=>
PMOs MoPpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4D5NVAvOi9{IN88US=> NX[4bpV3OjRiaB?= MV7EUXNQ MmrpZoxw[2u|IITo[UBqdmirYnn0bY9vKG:oIHPlcIwheHKxbHnm[ZJifGmxbjDwdo9lfWOnZDDifUBVT0ZvzsKx MUKyNlE4OzB3Mx?=
U87MG NVjpb5pqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlTiOU8yOCEQvF2= NGn3XpczKGh? MkjV[Y5p[W6lZYOgdoFlcW:|ZX7zbZRqfmm2eR?= MUSyNlAxPjl7OB?=
T98 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGDhOnE2NzFyIN88US=> M3rufFIhcA>? NEfjTI1mdmijbnPld{Bz[WSrb4PlcpNqfGm4aYT5 M4D2VVIzODB4OUm4
U87MG NH7GOolCeG:ydH;zbZMhSXO|YYm= NHGxfpAyOCEQvF2= MofjNkBp M3LiXIVvcGGwY3XzJJJi\GmjdHnvck1qdmS3Y3XkJGRPSSCmYX3h[4Uh[W6mIHHwc5B1d3OrczDyZZRmew>? M4rBfVIzODB4OUm4
NMA-23 M3vaS2Fxd3C2b4Ppd{BCe3OjeR?= NYjYPJlrOTBizszN MWWyJIg> MWnlcohidmOnczDyZYRq[XSrb36tbY5lfWOnZDDEUmEh\GGvYXflJIFv\CCjcH;weI9{cXNicnH0[ZM> NIfuOW0zOjByNkm5PC=>
HLE  NF7qcWRHfW6ldHnvckBCe3OjeR?= M17QNlAvODFvMUCwxsBvVQ>? MYm0PEBp NGTJTmNqdmirYnn0d{B1cGVibXnndoF1cW:wIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{ MVuyNFg1PDh5OB?=
HLF NEPRO3dHfW6ldHnvckBCe3OjeR?= NEXXfYsxNjBzLUGwNOKhdk1? M3nYV|Q5KGh? Moe5bY5pcWKrdIOgeIhmKG2rZ4LheIlwdiCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? M{XBT|IxQDR2OEe4
10A/HER2YVMA MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{O3cVAvOS1yLkWg{txO M2nudlkh\A>? NITJT5Bz\WS3Y3XzJJRp\SC|aYrlMEBqdn[jc3n2[Y5me3NiYX7kJINmdGxiboXtZoVzKG:oIHPvcI9vcWW| NX3WNZFIOjB|OEOxPVc>
MC38  MkPOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mnz5OUDPxE1? MXy1JIQ> NXPMV3hTcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUB1cW2nLXTldIVv\GWwdDDtZY5v\XJ? MmP6NVk6ODl5NES=
U937 MlnQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYDuV2VTPS1{MDFOwG0> MoC1NlQuPzJiaB?= NVTYc5hocW6qaXLpeJMh[2WubDDndo94fGhic3zp[4h1dHl? NHrI[nUyQDR7MkGxNy=>
HLE  NFyyUpdEgXSxdH;4bZR6KEG|c3H5 M3\4e|AvODBzLUKwJO69VQ>? Mnz5OFghcA>? M2HqS4lv\HWlZYOgZ4VtdCCleYTveI95cXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{ NYPLO3M2OTh|MUi0OFM>
HLF NILPSI5EgXSxdH;4bZR6KEG|c3H5 NIXZS5IxNjByMT2yNEDPxE1? MXy0PEBp M4i3eolv\HWlZYOgZ4VtdCCleYTveI95cXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{ MY[xPFMyQDR2Mx?=

... Click to View More Cell Line Experimental Data

In vivo試験 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]
臨床試験
特集

プロトコル (参考用のみ)

細胞アッセイ: [1]

細胞株 Colo357FG/GLT, and Colo357L3.6pl/GLT
濃度 Dissolved in DMSO, final concentrations ~10 μM
反応時間 48 hours
実験の流れ 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.

動物実験: [1]

動物モデル Athymic nude mice with orthotopic implantation of L3.6pl/GLT cells
製剤 Dissolved in the SX-1292 oral vehicle containing 1% sodium carboxymethylcellulose, 0.5% sodium lauryl sulfate, and 0.05% antifoam
投薬量 50 mg/kg
投与方法 Twice a day p.o.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download LY2109761 SDF
分子量 441.52
化学式

C26H27N5O2

CAS No. 700874-71-1
保管 3年-20℃
2年-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 2 mg/mL (4.52 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 0.5% CMC+0.25% Tween 80 16 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* 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.
化学名 7-(2-morpholinoethoxy)-4-(2-(pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl)quinoline

文献中の引用 (6)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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