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  MXnGeY5kfGmxbjDBd5NigQ>? MUexNOKh|ryPwrC= NHztOlkzKGh? NEKw[JFqdmirYnn0d{BifXSxcHjh[5khcW6mdXP0bY9vKGK7IHfhcIFv\2mw NXP2UXpCOjV{NkiwOFY>
PC-3 NWq1WVBHTnWwY4Tpc44hSXO|YYm= M4TJelAvOi9{L{Sg{txO MXmyOEBp NYrncWxbTE2VTx?= MWLpcohq[mm2czDUS2Yu|rJz4pETbY5lfWOnZDDTcYFlOiCjY4TpeoF1cW:w NUHTfWdOOjJzN{OwOVM>
PMOs MXjGeY5kfGmxbjDBd5NigQ>? NH;yXo4xNjJxMj:0JO69VQ>? NXu4RVRwOjRiaB?= NUW5RVVxTE2VTx?= MW\pcohq[mm2czDUS2Yu|rJz4pETbY5lfWOnZDDTcYFlOiCjY4TpeoF1cW:w NYTrU5doOjJzN{OwOVM>
PC-3 NXTIdHQ6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYKwMlIwOiEQvF2= MUmyOEBp MYPEUXNQ M2C0U4Jtd2OtczD0bIUhcW6qaXLpeIlwdiCxZjDj[YxtKHC{b3zp[oVz[XSrb36gdJJw\HWlZXSgZpkhXEeILd8yNS=> NUPLV|ZlOjJzN{OwOVM>
PMOs MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHfhZnExNjJxMjFOwG0> MV2yOEBp MWPEUXNQ MUnicI9kc3NidHjlJIlvcGmkaYTpc44hd2ZiY3XscEBxem:uaX\ldoF1cW:wIIDyc4R2[2WmIHL5JHRITi4QskG= M1jHTFIzOTd|MEWz
U87MG NGD1SXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NE[3NFc2NzFyIN88US=> MXiyJIg> MXzlcohidmOnczDyZYRqd3OnboPpeIl3cXS7 M2LPdFIzODB4OUm4
T98 NWDUPYRmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUi1M|ExKM7:TR?= NIXVRXIzKGh? NHPmZnRmdmijbnPld{Bz[WSrb4PlcpNqfGm4aYT5 Mnf0NlIxODZ7OUi=
U87MG M1fmeWFxd3C2b4Ppd{BCe3OjeR?= NGHMVVIyOCEQvF2= MnSzNkBp MWflcohidmOnczDyZYRq[XSrb36tbY5lfWOnZDDEUmEh\GGvYXflJIFv\CCjcH;weI9{cXNicnH0[ZM> NIfDTIMzOjByNkm5PC=>
NMA-23 Mo\vRZBweHSxc3nzJGF{e2G7 MX6xNEDPxE1? Mmq5NkBp MVrlcohidmOnczDyZYRq[XSrb36tbY5lfWOnZDDEUmEh\GGvYXflJIFv\CCjcH;weI9{cXNicnH0[ZM> NHfvUJYzOjByNkm5PC=>
HLE  NVvsT5ZFTnWwY4Tpc44hSXO|YYm= NEPT[HQxNjBzLUGwNOKhdk1? MY[0PEBp MWHpcohq[mm2czD0bIUhdWmpcnH0bY9vKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz M3XoUVIxQDR2OEe4
HLF MWLGeY5kfGmxbjDBd5NigQ>? M2PtSlAvODFvMUCwxsBvVQ>? MWq0PEBp NUfYd2hDcW6qaXLpeJMhfGinIH3p[5JifGmxbjDpckBiKGSxc3Wt[IVx\W6mZX70JI1idm6nch?= MnHrNlA5PDR6N{i=
10A/HER2YVMA M3S2cWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEPYeIIxNjFvMD61JO69VQ>? NH[4S2Q6KGR? NYS3bpp4emWmdXPld{B1cGVic3n6[UwhcW64YYPpeoVv\XO|IHHu[EBk\WyuIH71cYJmeiCxZjDjc4xwdmmncx?= NHy0V2IzODN6M{G5Oy=>
MC38  Ml7YS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH\TTWg2KM7:TR?= MXG1JIQ> NHrOXoJqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDhJJRqdWVvZHXw[Y5l\W62IH3hco5meg>? Mn;tNVk6ODl5NES=
U937 NHrZ[opIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkiyOU0zOCEQvF2= NVXsTIQ6OjRvN{KgbC=> Mn\wbY5pcWKrdIOgZ4VtdCCpcn;3eIghe2yrZ3j0cJk> MmDINVg1QTJzMUO=
HLE  MUPDfZRwfG:6aYT5JGF{e2G7 M{XxWFAvODBzLUKwJO69VQ>? NUjiepJYPDhiaB?= MmHVbY5lfWOnczDj[YxtKGO7dH;0c5hqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XJ? MlLhNVg{OTh2NEO=
HLF NV7UcHBlS3m2b4TvfIl1gSCDc4PhfS=> M{T6UVAvODBzLUKwJO69VQ>? NWTlflBsPDhiaB?= MUDpcoR2[2W|IHPlcIwh[3m2b4TvfIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? M1;LO|E5OzF6NESz

... 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 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 2 mg/mL (4.52 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
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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