LY2109761 化学構造
分子量: 441.52

高品質保証

カスタマーフィードバック(3)

MSDS

製品説明

  • Compare TGF-beta/Smad Inhibitors
    TGF-beta/Smad製品生物活性の比較
  • 研究分野

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  NYD2RY1PTnWwY4Tpc44hSXO|YYm= MljJNVDDqM7:TdMg NHXyb5kzKGh? NEXDW3dqdmirYnn0d{BifXSxcHjh[5khcW6mdXP0bY9vKGK7IHfhcIFv\2mw MoDZNlUzPjhyNE[=
PC-3 NGnlc4hHfW6ldHnvckBCe3OjeR?= NE[yb3IxNjJxMj:0JO69VQ>? NVzzXFNxOjRiaB?= M4nVUmROW09? NVzNUIx6cW6qaXLpeJMhXEeILd8yNgKBm2mwZIXj[YQhW22jZEKgZYN1cX[jdHnvci=> NFLjcYozOjF5M{C1Ny=>
PMOs NILlVWpHfW6ldHnvckBCe3OjeR?= M{[xe|AvOi9{L{Sg{txO NFL6fI8zPCCq NFHofHZFVVOR M3WwdolvcGmkaYTzJHRITi4QskJihLNqdmS3Y3XkJHNu[WR{IHHjeIl3[XSrb36= NIP2b3kzOjF5M{C1Ny=>
PC-3 NIXYRWJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHHHT2gxNjJxMjFOwG0> MVOyOEBp NIDQTJRFVVOR M{m4VIJtd2OtczD0bIUhcW6qaXLpeIlwdiCxZjDj[YxtKHC{b3zp[oVz[XSrb36gdJJw\HWlZXSgZpkhXEeILd8yNS=> NIe4fYozOjF5M{C1Ny=>
PMOs MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEixRYgxNjJxMjFOwG0> MU[yOEBp NWDj[VZ2TE2VTx?= NUjnXnpM[myxY3vzJJRp\SCrbnjpZol1cW:wIH;mJINmdGxicILvcIln\XKjdHnvckBxem:mdXPl[EBjgSCWR1[t{tIy MXqyNlE4OzB3Mx?=
U87MG NIqyOYxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoX0OU8yOCEQvF2= NIDtU4szKGh? M1zsT4VvcGGwY3XzJJJi\Gmxc3Xud4l1cX[rdIm= MUOyNlAxPjl7OB?=
T98 M13JU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVS1M|ExKM7:TR?= MWmyJIg> NF3QXm5mdmijbnPld{Bz[WSrb4PlcpNqfGm4aYT5 M3Lo[VIzODB4OUm4
U87MG NIDQRmdCeG:ydH;zbZMhSXO|YYm= Ml7XNVAh|ryP MUGyJIg> MXLlcohidmOnczDyZYRq[XSrb36tbY5lfWOnZDDEUmEh\GGvYXflJIFv\CCjcH;weI9{cXNicnH0[ZM> MoDoNlIxODZ7OUi=
NMA-23 MkHJRZBweHSxc3nzJGF{e2G7 Mn7aNVAh|ryP MmSwNkBp M1fITYVvcGGwY3XzJJJi\GmjdHnvck1qdmS3Y3XkJGRPSSCmYX3h[4Uh[W6mIHHwc5B1d3OrczDyZZRmew>? MYGyNlAxPjl7OB?=
HLE  MVzGeY5kfGmxbjDBd5NigQ>? NWHJOGxHOC5yMT2xNFDDqG6P MnLzOFghcA>? NEXteI1qdmirYnn0d{B1cGVibXnndoF1cW:wIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{ M4W4WVIxQDR2OEe4
HLF MVvGeY5kfGmxbjDBd5NigQ>? NV\WcJdQOC5yMT2xNFDDqG6P MlT3OFghcA>? NEPGb4NqdmirYnn0d{B1cGVibXnndoF1cW:wIHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{ MkDVNlA5PDR6N{i=
10A/HER2YVMA M{LxVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUTYUmd2OC5zLUCuOUDPxE1? NWTUfHU6QSCm M3G2RpJm\HWlZYOgeIhmKHOrenWsJIlvfmG|aY\lcoV{eyCjbnSgZ4VtdCCwdX3i[ZIhd2ZiY3;sc45q\XN? NYLrVlQ{OjB|OEOxPVc>
MC38  NXrxcHhDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mm[5OUDPxE1? MYe1JIQ> Ml\0bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYTD0bY1mNWSncHXu[IVvfCCvYX7u[ZI> NYTZS|BvOTl7MEm3OFQ>
U937 MoHPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUjxXFhoPS1{MDFOwG0> NWe1NoU6OjRvN{KgbC=> M1PjNolvcGmkaYTzJINmdGxiZ4Lve5RpKHOuaXfoeIx6 Mmr2NVg1QTJzMUO=
HLE  NELVdYlEgXSxdH;4bZR6KEG|c3H5 M2D5cVAvODBzLUKwJO69VQ>? MkPHOFghcA>? M4HaXolv\HWlZYOgZ4VtdCCleYTveI95cXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{ NYrjeIhDOTh|MUi0OFM>
HLF MkD6R5l1d3SxeHn0fUBCe3OjeR?= MonSNE4xODFvMkCg{txO MWO0PEBp M3XCZYlv\HWlZYOgZ4VtdCCleYTveI95cXS7IHnuJIEh\G:|ZT3k[ZBmdmSnboSgcYFvdmW{ NXS5RYVpOTh|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)

技術サポート&よくある質問(FAQ)

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の質問がある場合は、お気軽くお問合せください。

* 必須

Related TGF-beta/Smad 阻害剤

  • SD-208

    SD-208は1種のセレクティブTGF-βRI (ALK5)阻害剤です。このIC50値は48 nMです。選択性について、TGF-βRI (ALK5)はTGF-βRIIより100倍以上が高くなります。

  • LDN-214117

    LDN-214117は1種の有効的でセレクティブBMP I型受容体キナーゼALK2阻害剤です。このIC50値は24 nMです。

  • SB431542

    SB431542 は ALK5を抑制する時IC50が94 nMになる.

  • LDN-193189

    LDN-193189は、ALK2ALK3の選択的な阻害剤で、IC50がそれぞれ5 nMと30 nMです。

  • Galunisertib (LY2157299)

    Galunisertib (LY2157299)は、強力なTβRIとTβRII(トランスフォーミング成長因子βレセプターIおよびII)阻害剤で, IC50がそれぞれ86 nM と 2 nMです。

  • SB525334

    SB525334 は有効な選択を転化成長因子-β1(TGF -β1)受容体(活性化素受容体類キナーゼ5、ALK5)、IC50 が14.3 nMになる.

  • RepSox

    RepSox is a potent and selective inhibitor of the TGFβ/ALK5 with IC50 of 23 nM.

  • Pirfenidone

    Pirfenidone is an inhibitor for TGF-β production and TGF-β stimulated collagen production, also reduces production of TNF-α and IL-1β, has anti-fibrotic and anti-inflammatory properties. Phase 3.

  • DMH1

    DMH1は1種のセレクティブBMP受容体阻害剤で、ALK2を抑制します。このIC50値は107.9 nMになります。尚、DMH1はAMPK、 ALK5、KDR (VEGFR-2)とPDGFRに抑制効果を与えません。

最近チェックしたアイテム

Tags: LY2109761を買う | LY2109761供給者 | LY2109761を購入する | LY2109761費用 | LY2109761生産者 | オーダーLY2109761 | LY2109761代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
お問い合わせ