FL-411-BRD4-IN-1-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEFL-411Cat. No.: HY-111102CAS No.: 2118944-88-8Synonyms: BRD4-IN-1分式: CHNOS分量: 341.43作靶点: Epigenetic Reader Domain作通路: Epigenetics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 : 5.4 mg/mL (1

2、5.82 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 1.25 mg/mL (3.66 mM); Suspended solution; Need ultrasonic2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 1.25 mg/mL (3.66 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE

3、BIOLOGICAL ACTIVITY物活性 FL-411种有效的选择性 BRD4 抑制剂，抑制 BRD4(1)，IC50 为 0.430.09 M。IC50 & Target BRD4(1)0.43 M (IC50)体外研究 FL-411 is a selective BRD4 inhibitor. Binding affinities of FL-411 are measured by TR-FRET against the firstand second bromodomains of BRD2(1), BRD4(1), and BRD4(2) with IC50s of 24.600.

4、70 M, 0.470.02 M,0.930.05 M, respectively. FL-411 possesses a good BRD4(1) inhibition activity (IC50=0.430.09 M),antiproliferative activity (MCF-7, IC50=1.620.06 M; MDA-MB-231, IC50=3.270.14 M), and autophagicactivity (42.29% in MCF-7 cells), as well as displays a low toxicity against MCF10A cells).

5、 FL-411 inducesATG5-dependent autophagy-associated cell death (ACD) by blocking BRD4-AMPK interaction and thusactivating AMPK-mTOR-ULK1-modulated autophagic pathway in breast cancer cells 1.体内研究 To evaluate the antitumor activity of FL-411 in vivo, two breast tumor xenograft models, namely, MCF-7 an

6、dMDA-MB-231 cell lines models, are used. The in vivo study is conducted using three different doses of FL-411: 25 mg/kg, 50 mg/kg, and 100 mg/kg. In all the models, FL-411 shows significant tumor growth inhibitionin a dose-dependent manner as determined by 80% and 76% tumor growth inhibition ratio i

7、n MCF-7 andMDA-MB-231 cell models, respectively. A remarkable loss of tumor weights is observed in all dose groups (p1.PROTOCOLCell Assay 1 The MCF-7 and MDA-MB-231 cells are dispensed in 96-well flat bottom microtiter plates at a density of5104 cells/mL. After 24 h incubation, MCF-7 or MDA-MB-231 c

8、ells are treated with 1.5 and 3 M FL-411,respectively. 3-MA (1 mM) is added 1 h before treated with FL-411. After treatment, cell viability is measuredby the MTT assay. 5 mg/mL MTT is added to each well. After 4 h incubation, the medium is removed and150 L of DMSO is added to each well to dissolve t

9、he crystal formazan dye. Absorbance is measured at 570nm on an enzyme-linked immunosorbent assay reader 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administration 1 52 female nude mice (BALB/c, 6-8 weeks, 20-22 g) are injected subcuta

10、neously with MCF-7 cells or MDA-MB-231 cells (5106 cells/mouse), respectively. When the tumors reach 100 mm3 in volume, the mice aredivided into four groups for each cell line. Three groups are treated with different doses of FL-411 (low dose,25 mg/kg; median dose, 50 mg/kg; high dose, 100 mg/kg) on

11、ce a day by intragastric administration for 24 or27 days, whereas the control group is treated with vehicle control. During the treatment, the tumor volumesand body weight are measured every 3 days until the end of the study. At the end of treatment, all mice aresacrificed. The tumor tissues are har

12、vested, weighed, and photographed. Then, the tumor tissues are frozenin liquid nitrogen or fixed in formalin immediately 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEREFERENCES1. Ouyang L, et al. Discovery of a Small-Molecule Bromodomain-Containing Protein 4 (BRD4) Inhibitor That InducesAMP-Activated ProteinKinase-Modulated Autophagy-Associated Cell Death in Breast Cancer. J Med Chem. 2017 Dec 28;60(24):9990-10012.McePdfHeigh