LY2109761 - TGF-β Receptor 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELY2109761Cat. No.: HY-12075CAS No.: 700874-71-1分式: CHNO分量: 441.52作靶点: TGF- Receptor; Autophagy作通路: TGF-beta/Smad; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 30 mg/mL (67.95 mM

2、)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.2649 mL 11.3245 mL 22.6490 mL5 mM 0.4530 mL 2.2649 mL 4.5298 mL10 mM 0.2265 mL 1.1325 mL 2.2649 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实

3、验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.08 mg/mL (4.71 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.08 mg/mL (4.71 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1

4、/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.08 mg/mL (4.71 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 LY2109761可服，选择性的 TGF- receptor type I/II 抑制剂，Ki分别为38 nM 和 300 nM。IC50 & Target Ki: 38 nM (TRI), 300 nM (TRII)体外研究 LY2109761 significantly inhibits the growth of L3.6pl/GLT soft agar

5、 colonies in a dose-dependent manner,and results in appr 33% inhibition at 2 M and 73% inhibition at 20 M. Targeting TRI/II kinase activity withLY2109761 (5 M) almost completely suppresses both the basal and TGF-1-stimulated migration ofL3.6pl/GLT cells 1. LY2109761 induces a dose-dependent reductio

6、n in phosphorylation of Smad-2. HLEendogenous phosphorylation of Smad-2 is inhibited by LY2109761. LY2109761 blocks migration on differentECM proteins and invasion of both HLE and HLF through a 3-dimensional structure. LY2109761 increases E-cadherin mRNA expression after 24 hours and protein levels

7、after 48 hours 2. LY2109761 pretreatmentreduces clonogenic survival in cell cultures of U87MG and T98 following radiation, resulting in an increase inthe radiosensitivity with a DEF0.1 of 1.30 and 1.37, respectively 3.体内研究 LY2109761 (50 mg/kg, p.o.) greatly reduces the tumor volume and increases the

8、 median survival duration ofthe mice to 45.0 days. The mice treated with LY2109761 develop significantly fewer metastatic lesions and,in some of them, no metastatic lesion, as indicated by the GFP signal, can be identified in the abdomen 1.LY2109761 enhances radiation-induced tumor growth delay in a

9、 U87MG subcutaneous xenograft tumormodel in BALB/c nude mice. LY2109761 increases survival in an orthotopical CSLC glioblastoma model andenhanced antitumor activity of radiation 2.PROTOCOLCell Assay 1 L3.6pl/GLT cells are washed twice with cold PBS and lysed at 4C into RIPA buffer (50 mM Tris HCl pH

10、 8,150 mM NaCl, 1% NP-40, 0.5% sodium deoxycolate, and 0.1% SDS). Tumor and liver specimens arehomogenized into RIPA buffer with an electric homogenizer and then maintained in constant agitation for twohours at 4C. The lysates are cleared by centrifugation. Each lysate (20 g of protein) is separated

11、 by 8%SDSand probed with polyclonal rabbit antibodies against total ERK1/2, TRI, and TRII or withmonoclonal mouse antibodies against phosphorylated Smad2, total Smad2, phosphorylated ERK1/2, andphosphorylated and total JNK. Immunoreactive proteins are visualized with Lumi-Light Western blottingsubst

12、rate according to the manufacturers instructions. phosphorylated Smad2/Smad2 band density ratiosare calculated using the ImageQuant software.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Fifty mice are randomLy allocated into five groups (n=5 m

13、ice per group) to receive p.o. vehicle for 50 L ofAdministration 1 LY2109761 or 50 mg/kg LY2109761 twice a day p.o. On day 0, mice are anesthetized with 1.5% isofluorane-air mixture, a small left abdominal flank incision is created, and the spleen is carefully exteriorized.L3.6pl/GLT or C5LM2/GLT ce

14、lls (1.0105 cells/50 L of HBSS), cultured in the presence of LY2109761 (5 2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEM) or DMSO from day 5 to day 0, are inoculated into the spleen with a 30-gauge needle. A visible paling ofthe spleen is the criterion for successful inoculation. After 10 min, t

15、he spleen is removed using a high-temperature cautery to avoid the possibility that the ectopic growth of pancreatic tumor cells in the spleencould be a confounding source of hematogenous liver metastatic cells. The abdominal wall is closed in onelayer with wound clips. Treatment with 50 mg/kg LY210

16、9761 twice a day p.o. (days 1-5 of each week afterinoculation) is continued for one group of untreated mice inoculated with untreated cells.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 J Hepatol. 2015 Oct;63(4):863-73. Nat Commun. 2017 Au

17、g 18;8(1):286. J Dent Res. 2019 Jun 12:22034519854734. Biochim Biophys Acta Mol Basis Dis. 2018 Nov;1864(11):3824-3836. J Cell Biochem. 2019 Jun.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Melisi D, et al. LY2109761, a novel transforming growth factor beta receptor type I a

18、nd type II dual inhibitor, as a therapeutic approach tosuppressing pancreatic cancer metastasis. Mol Cancer Ther, 2008, 7(4), 829-840.2. Fransvea E, et al. Blocking transforming growth factor-beta up-regulates E-cadherin and reduces migration and invasion ofhepatocellular carcinoma cells. Hepatology, 2008, 47(5), 1557-1566.3. Zhang M, et al. Blockade of TGF- signaling by the TGFR-I kinase inhibitor LY2109761 enhances radiation resp