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  MlzBSpVv[3Srb36gRZN{[Xl? NWWxeYdXOTEEoN88UeKh NYXpemZZOiCq MYXpcohq[mm2czDheZRweGijZ4mgbY5lfWO2aX;uJIJ6KGejbHHu[4lv NG\CTmIzPTJ4OEC0Oi=>
PC-3 NWXmfVFUTnWwY4Tpc44hSXO|YYm= NVvtWIpMOC5{L{KvOEDPxE1? MWSyOEBp NWrwd4pNTE2VTx?= NHHVUGlqdmirYnn0d{BVT0ZvzsKx5qCUcW6mdXPl[EBUdWGmMjDhZ5RqfmG2aX;u MkPnNlIyPzNyNUO=
PMOs MkP3SpVv[3Srb36gRZN{[Xl? M3XLdFAvOi9{L{Sg{txO M3XIO|I1KGh? M3r2VGROW09? NIGwRm5qdmirYnn0d{BVT0ZvzsKx5qCUcW6mdXPl[EBUdWGmMjDhZ5RqfmG2aX;u M{PBclIzOTd|MEWz
PC-3 Ml3PS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV3qZYZHOC5{L{Kg{txO Moi4NlQhcA>? MUfEUXNQ M33S[oJtd2OtczD0bIUhcW6qaXLpeIlwdiCxZjDj[YxtKHC{b3zp[oVz[XSrb36gdJJw\HWlZXSgZpkhXEeILd8yNS=> M4DMRVIzOTd|MEWz
PMOs M3TGcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M121SlAvOi9{IN88US=> M3HHNVI1KGh? M{WyN2ROW09? MVjicI9kc3NidHjlJIlvcGmkaYTpc44hd2ZiY3XscEBxem:uaX\ldoF1cW:wIIDyc4R2[2WmIHL5JHRITi4QskG= NVLiUIFwOjJzN{OwOVM>
U87MG NVWwOJF{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYC1M|ExKM7:TR?= NIfjeoIzKGh? MXTlcohidmOnczDyZYRqd3OnboPpeIl3cXS7 NV\3UmtUOjJyME[5PVg>
T98 MkToS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGS2N|E2NzFyIN88US=> M2\sclIhcA>? NH\LVmhmdmijbnPld{Bz[WSrb4PlcpNqfGm4aYT5 MlXFNlIxODZ7OUi=
U87MG NHfxRotCeG:ydH;zbZMhSXO|YYm= NGLkTG8yOCEQvF2= M1v2VFIhcA>? NYLmTYdp\W6qYX7j[ZMhemGmaXH0bY9vNWmwZIXj[YQhTE6DIHThcYFo\SCjbnSgZZBweHSxc3nzJJJifGW| M4D2R|IzODB4OUm4
NMA-23 MkPaRZBweHSxc3nzJGF{e2G7 MVqxNEDPxE1? M3vXcVIhcA>? NXfwS|JK\W6qYX7j[ZMhemGmaXH0bY9vNWmwZIXj[YQhTE6DIHThcYFo\SCjbnSgZZBweHSxc3nzJJJifGW| MX6yNlAxPjl7OB?=
HLE  MkjrSpVv[3Srb36gRZN{[Xl? MUCwMlAyNTFyMNMgcm0> NVHQOYE6PDhiaB?= M{nFS4lvcGmkaYTzJJRp\SCvaXfyZZRqd25iaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XJ? NHvUUnozODh2NEi3PC=>
HLF NYrpZYN1TnWwY4Tpc44hSXO|YYm= MojXNE4xOS1zMEFCpI5O NYPW[XRNPDhiaB?= NH3QdZRqdmirYnn0d{B1cGVibXnndoF1cW:wIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{ NVLpb3dOOjB6NES4O|g>
10A/HER2YVMA MkLQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVqwMlEuOC53IN88US=> MVe5JIQ> MkXqdoVlfWOnczD0bIUhe2m8ZTygbY53[XOrdnXu[ZN{KGGwZDDj[YxtKG63bXLldkBw\iClb3zvcolmew>? NVTF[WhIOjB|OEOxPVc>
MC38  MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFr4TWI2KM7:TR?= NVHVZYVkPSCm NW\STWVIcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZUB1cW2nLXTldIVv\GWwdDDtZY5v\XJ? Mn;XNVk6ODl5NES=
U937 NWqyfFlsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGLGO242NTJyIN88US=> NYnTfpJEOjRvN{KgbC=> MmrJbY5pcWKrdIOgZ4VtdCCpcn;3eIghe2yrZ3j0cJk> MmXlNVg1QTJzMUO=
HLE  NV;ublNnS3m2b4TvfIl1gSCDc4PhfS=> NFGwfHoxNjByMT2yNEDPxE1? M13kVVQ5KGh? MVPpcoR2[2W|IHPlcIwh[3m2b4TvfIl1gSCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>? MVuxPFMyQDR2Mx?=
HLF MVnDfZRwfG:6aYT5JGF{e2G7 NGfBTXIxNjByMT2yNEDPxE1? NIDqSoo1QCCq MnTpbY5lfWOnczDj[YxtKGO7dH;0c5hqfHliaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XJ? NVv2VI1ROTh|MUi0OFM>

... 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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