ホームページ TGF-beta/Smad TGF-beta/Smad inhibitor - Autophagy inhibitor - Apoptosis related activator LY2109761 For research use only.

LY2109761

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化学構造

CAS No. 700874-71-1

サイズ 価格(税別) 在庫状況
10mM (1mL in DMSO) JPY 59500 国内在庫あり
JPY 40500 国内在庫あり
JPY 145500 国内在庫あり
JPY 295500 国内在庫あり
JPY 748500 国内在庫なし(納期7~10日)

代表番号: 045-509-1970|電子メール：[email protected]
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LY2109761と併用されることが多い化合物

Galunisertib (LY2157299)

LY2109761 and Galunisertib target TGF-β receptor I and exhibit anti-tumor activity.

Herbertz S, et al. Drug Des Devel Ther. 2015 Aug 10;9:4479-99.

LY2109761関連製品

シグナル伝達経路

TGF-beta/Smad Signaling Pathways

TGF-beta/Smadシグナル伝達経路

TGF-beta/Smad阻害剤の選択性比較

Cell Data

Cell Lines Assay Type Concentration Incubation Time 活性情報 PMID
HLE  Function Assay 0.01-100 nM 48 h inhibits the migration in a dose-dependent manner 20844878
NMA-23 Apoptosis Assay 10 μM 2 h enhances radiation-induced DNA damage and apoptosis rates 22006998
U87MG Apoptosis Assay 10 μM 2 h enhances radiation-induced DNA damage and apoptosis rates 22006998
T98 Growth Inhibition Assay 5/10 μM 2 h enhances radiosensitivity 22006998
U87MG Growth Inhibition Assay 5/10 μM 2 h enhances radiosensitivity 22006998
PMOs Growth Inhibition Assay 0.2/2 μM 24 h blocks the inhibition of cell proliferation produced by TGF-β1 22173053
PC-3 Growth Inhibition Assay 0.2/2 μM 24 h blocks the inhibition of cell proliferation produced by TGF-β1 22173053
PMOs Function Assay 0.2/2/4 μM 24 h inhibits TGF-β1–induced Smad2 activation 22173053
PC-3 Function Assay 0.2/2/4 μM 24 h inhibits TGF-β1–induced Smad2 activation 22173053
HepG2  Function Assay 10 μM  2 h inhibits autophagy induction by galangin 25268046
HLF Function Assay 0.01-100 nM 48 h inhibits the migration in a dose-dependent manner 20844878
10A/HER2YVMA Growth Inhibition Assay 0.1-0.5 μM 9 d reduces the size, invasiveness and cell number of colonies 20383197
MC38  Growth Inhibition Assay 5 μM 5 d inhibits cell growth in a time-dependent manner 19909744
U937 Growth Inhibition Assay 5-20 μM 24-72 h inhibits cell growth slightly 18492113
HLE  Cytotoxity Assay 0.001-20 μM 48 h induces cell cytotoxity in a dose-dependent manner 18318443
HLF Cytotoxity Assay 0.001-20 μM 48 h induces cell cytotoxity in a dose-dependent manner 18318443
Sf9 Function assay 1 hr Inhibition of human His-tagged TGFbetaR1 T204D mutant expressed in Sf9 insect cells after 1 hr by HTRF assay, IC50 = 0.0037 μM. 29422332
T-cells Function assay 1 hr Inhibition of TGFbetaR1 in human primary T-cells assessed as TGFbeta-stimulated PSMAD phosphorylation preincubated for 1 hr followed by TGFbeta addition measured after 90 mins by Alpha screen assay, IC50 = 0.37 μM. 29422332
Mv1Lu Function assay 1 hr Inhibition of TGFbetaR1 in mink Mv1Lu cells assessed as TGFbeta-stimulated PSMAD2 phosphorylation preincubated for 1 hr followed by TGFbeta addition measured after 15 mins, IC50 = 0.75 μM. 29422332
Sf9 Function assay Inhibition of TGFbeta type receptor 1 ALK5 (T204D) expressed in Sf9 cells, IC50 = 0.069 μM. 18314943
Mv1Lu-p3TP-Lux Antiproliferative assay Antiproliferative activity against mink Mv1Lu-p3TP-Lux cells by luciferase reporter assay, IC50 = 0.18 μM. 18314943
NIH3T3 Antiproliferative assay Antiproliferative activity against mouse NIH3T3 cells by [3H]thymidine assay, IC50 = 0.21 μM. 18314943
Calu6 Function assay Inhibition of TGFbeta type receptor 1 in orally dosed human Calu6 cells xenografted mouse by IVTI pharmacokinetic assay, EC50 = 0.236 μM. 18314943
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生物活性

製品説明 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
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 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]
細胞実験 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.
実験結果図 Methods Biomarkers 結果図 PMID
Western blot p-Smad2 / Smad E-cadherin β-catenin / MMP-9 / MMP-2 / nm23 / uPA / COX-2 CDK2 / CDK4 / Cyclin D1 / p-Rb 29416682
In Vivo
In Vivo

Administration of LY2109761 (50 mg/kg) alone or in combination 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]
動物実験 動物モデル Athymic nude mice with orthotopic implantation of L3.6pl/GLT cells
投与量 50 mg/kg
投与経路 Twice a day p.o.

化学情報

分子量 441.52 化学式

C26H27N5O2
CAS No. 700874-71-1 SDF Download LY2109761 SDFをダウンロードする
Smiles C1CC2=C(C(=NN2C1)C3=CC=CC=N3)C4=C5C=CC(=CC5=NC=C4)OCCN6CCOCC6
保管

In vitro
Batch:

DMSO : 9 mg/mL ( (20.38 mM)； 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量 濃度 体積 分子量

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

mg/kg g μL 匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH2O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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Handling Instructions

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