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)

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LY2109761と併用されることが多い化合物

Galunisertib (LY2157299)

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

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
(Cell-free assay)		 TβRII
(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 this compound 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. This chemical 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. It pretreatment enhances radiosensitivity of glioblastoma cells via TGF-β signaling blockage. This compound reduces the self-renewal and proliferation of GBM-derived cancer stem–like cells (CSLC), which can be significantly enhanced when combined with radiation.

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 this compound 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 S2704-WB1.gif 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. In consistent with the in vitro effect, administration of this compound 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.

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.
  • https://pubmed.ncbi.nlm.nih.gov/18413796/
  • https://pubmed.ncbi.nlm.nih.gov/18318443/
  • https://pubmed.ncbi.nlm.nih.gov/22006998/

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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