FL-411

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Chemical Structure| 2118944-88-8 同义名 : BRD4-IN-1
CAS号 : 2118944-88-8
货号 : A515782
分子式 : C18H19N3O2S
纯度 : 99%+
分子量 : 341.43
MDL号 : MFCD31657378
存储条件：

Pure form Keep in dark place, sealed in dry, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 4 mg/mL(11.72 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
生物活性
靶点

  • BET

    BRD4(1), IC50:0.43 μM
描述 Bromodomain-containing protein 4 (BRD4) belongs to the bromodomain and extra-terminal (BET) protein family, functions as an epigenetic and transcriptional regulatory. FL-411 shows potent inhibitory activity against BRD4 with an IC50 value of 0.43 µM. It also inhibited the proliferation of MCF-7 cells and MDA-MB-231 cells with IC50 values of 1.62 μM and 3.27 μM, respectively. In MCF-7 and MDA-MB-231 cells treated with 1.5 or 3 μM FL-411, the expression of BRD4 and its downstream target c-Myc were greatly inhibited as compared to the control group, whereas the phosphorylation of AMPKα at thr172 site was activated. FL-411 also augmented the interaction between p53 and AMPK, but attenuated the interaction between BRD4 and p53 in MCF-7 cells. FL-411 at 1.5 or 3 μM downregulated the expression levels of p-Akt (ser473), p-Akt (thr308), and p-mTOR (ser2448) in MCF-7 or MDA-MB-231 cells, while the expressions of Akt and mTOR remained unchanged. The administration of FL-411 (25, 50, and 100 mg/kg) resulted in 80% and 76% tumor growth inhibition in mice models inoculated with MCF-7 or MDA-MB-231 cells, respectively, in a dose-dependent manner. FL-411-treated animals also showed reduced number of Ki-67 positive cells and increased LC3 expression in the tumor tissues[1].
作用机制 FL-411 is a potent and selective inhibitor of BRD4. The 3,5-dimethylphenol moiety of FL-411 penetrated into the N-acetylated lysine pocket of the enzyme, forming a direct hydrogen bond. The residues Gln85 and Pro82 contribute to the selectivity of FL-411 over BRD4.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.93mL

0.59mL

0.29mL

14.64mL

2.93mL

1.46mL

29.29mL

5.86mL

2.93mL
参考文献

[1]Ouyang L, Zhang L, Liu J, Fu L, Yao D, Zhao Y, Zhang S, Wang G, He G, Liu B. Discovery of a Small-Molecule Bromodomain-Containing Protein 4 (BRD4) Inhibitor That Induces AMP-Activated Protein Kinase-Modulated Autophagy-Associated Cell Death in Breast Cancer. J Med Chem. 2017 Dec 28;60(24):9990-10012. doi: 10.1021/acs.jmedchem.7b00275. Epub 2017 Dec 7. PMID: 29172540.