NSC305787-hydrochloride - Ezrin 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemENSC305787 hydrochlorideCat. No.: HY-18931ACAS No.: 53868-26-1分式: CHClNO分量: 481.89作靶點(diǎn): Others作通路: Others儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 8 mg/mL (16.60 mM; Need ultrasonic and

2、 warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.0752 mL 10.3758 mL 20.7516 mL5 mM 0.4150 mL 2.0752 mL 4.1503 mL10 mM 0.2075 mL 1.0376 mL 2.0752 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 NSC305787 hydrochloride種 ezrin 抑制劑，Kd 值為 5.85 M，抑制 PKC 導(dǎo)致的 ezrin 磷酸化，IC50

3、of 8.3 M，具有抗腫瘤活性。IC50 & Target Kd: 5.85 M (ezrin) 1IC50: 8.3 M (ezrin) 1體外研究NSC305787 hydrochloride is an inhibitor of ezrin with a Kd of 5.85 M, and has antitumor activity.1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemENSC305787 inhibits PKC phosphorylation of Ezrin, Moesin, Radixin, MBP, with IC

4、50s of 8.3, 9.4, 55, 58.9 M, respectively. NSC305787 binds to PKC with a Kd value of 172.4 M, and inhibits ezrin T567phosphorylation primarily via its binding to ezrin and not through inhibition of PKC kinase activity.NSC305787 (1, 10 M) shows inhibitory activity against ezrin-mediated invasion of K

5、7M2 osteosarcoma (OS)cells. Moreover, NSC305787 (10 M) reduces cell motility phenotypes in zebrafish and blocks OS metastaticgrowth in lung organ culture 1.體內(nèi)研究 NSC305787 (0.240 mg/kg/day, i.p.) suppresses ezrin-dependent osteosarcoma metastatic growth in mouselung 1. NSC305787 (240 g/kg, i.p.) dram

6、atically inhibits pulmonary metastasis in a transgenic mousemodel of osteosarcoma (Osx-Cre+p53fl/flpRBfl/fl) and shows a more favorable pharmacokinetic profilecompared with NSC668394 in the mouse model 2.PROTOCOLCell Assay 1 Human umbilical vein endothelial cells (HUVECs; 2.5 104/well) are seeded in

7、 a 96-well plate in endothelialgrowth media-2. Following formation of a confluent HUVEC monolayer (-32 h), endothelial growth media-2 isaspirated and a layer of osteosarcoma (OS) cells (1.0 104 cells/well) is added to Dulbeccos modified Eaglemedium containing NSC305787. This specific time point is a

8、ccepted as 0 h of treatment, and invasion ismonitored during the subsequent 5 h by measuring changes in resistance at the cell-electrode interphase.The cell index is calculated according to the following formula: cell index = (Rt R0)/F, where Rt is resistanceat time point t, R0 is background resista

9、nce (measured with media alone, no cells) and F is frequency atwhich the measurement is taken (10 kHz) 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 The Osx-Cre+p53fl/flpRBfl/fl transgenic mouse model of osteosarcoma is

10、 used in the assay. Mice are treatedwith 240 g/kg/day NSC305787, 226 g/kg/day NSC668394, or vehicle (DMSO, 1%) once daily, five times aweek by i.p. injection in a volume of 100 L. At the end of the study, lung and tumor samples are isolatedupon necropsy. Half of each sample is flash frozen immediate

11、ly in liquid nitrogen, and the other half is fixedin 10% formalin for 18-24 h, transferred to 70% ethanol, and stored at room temperature 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) PLoS Pathog. 2019 May 9;15(5):e1007737.See more custo

12、mer validations on HYPERLINK / www.MedChemEREFERENCES1. Bulut G, et al. Small molecule inhibitors of ezrin inhibit the invasive phenotype of osteosarcoma cells. Oncogene. 2012 Jan19;31(3):269-81.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE2. elik H, et al. Ezrin Inhibition Up-regulates Stress Response Gene Expression. J Biol Chem. 2016 Jun 17;291(25):13257-70.McePdfHeightCaution