LY364947

製品コードS2805 バッチS280502

印刷

化学情報

Chemical Structure Synonyms HTS 466284 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C17H12N4
分子量 272.3 CAS No. 396129-53-6
Solubility (25°C)* 体外 DMSO 20 mg/mL (73.44 mM)
Water Insoluble
Ethanol Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 LY364947 (HTS 466284) is a potent ATP-competitive inhibitor of TGFβR-I with IC50 of 59 nM in a cell-free assay, shows 7-fold selectivity over TGFβR-II.
in vitro LY364947 is an ATP competitive and tight-binding inhibitor, inhibiting phosphorylation of P-Smad3 by TGFβR-I kinase with Ki of 28 nM. LY364947 inhibits in vivo Smad2 phosphorylation within the NMuMg cells with IC50 of 135 nM. LY364947 reverses TGF-β-mediated growth inhibition in NMuMg cells with IC50 of 0.218 μM. LY364947 potentiates the xVent2-lux BMP4 response in NMuMg cells by 30% at concentrations as low as 0.25 μM. LY364947 (2 μM) prevents TGF-β-induced epithelial−mesenchymal transition in NMuMg cells. [3] LY364947 (3 μM) induces expression of Prox1 and LYVE-1 in almost all HDLECs after 24 hours. [4] LY364947 promotes nuclear export of Foxo3a, with low Smad2/3 and high Akt phosphorylation levels in leukaemia-initiating cells. LY364947 (< 20 μM) suppresses leukaemia-initiating cells colony-forming ability after co-culture with OP-9 stromal cells. [5]
in vivo LY364947 (1 mg/kg i.p.) accelerates lymphangiogenesis, as evidence by significantly increased the LYVE-1-positive areas, in a mouse model of chronic peritonitis. LY364947 (1 mg/kg i.p.) significantly increases the LYVE-1-positive areas in tumor tissues in tumor xenograft models using BxPC3 pancreatic adenocarcinoma cells. [4] LY364947 (25 mg /kg) increases p-Akt and decreases nuclear Foxo3a in leukaemia-initiating cells in CML-affected mice. [5]

プロトコル(参考用のみ)

キナーゼアッセイ Filter-binding assay
The IC50 of LY364947 at different enzyme concentrations are determined by the filter-binding assay. Typically, 40 μL reactions in 50 mM HEPES at pH 7.5, 1 mM NaF, 200 μM pKSmad3(−3), and 50 mM ATP containing a titration of each inhibitor with concentrations of 1600, 800, 400, 200, 100, 50, 25, and 0 nM are incubated at 30 °C for 30 min. The IC50 is calculated using a nonlinear regression method with GraphPad Prism software. The binding type is determined by plotting the correlation between enzyme concentrations and IC50 values.
細胞アッセイ 細胞株 HOXB9-MCF10A cells
濃度 10 μM
反応時間 24 h
実験の流れ

HOXB9-MCF10A cells were treated with 10 μM LY364947 for 24 h. Proteins were analyzed for phospho-Smad2 and total Smad2 levels
動物実験 動物モデル Tumor xenograft models with BxPC3 pancreatic adenocarcinoma cells.
投薬量 1 mg/kg
投与方法 Intraperitoneally administrated 3 times a week for 3 weeks.

カスタマーフィードバック

Data from [Chem Biol Interact, 2014, 217, 1-8]

Data from [Data independently produced by , , Nat Commun, 2016, 7:12047]

Data from [Data independently produced by , , Cancer Lett, 2017, 403:86-97]

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An epithelial-mesenchymal plasticity signature identifies two novel LncRNAs with the opposite regulation [ Front Cell Dev Biol, 2022, 10:885785] PubMed: 36120580

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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