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Y06036

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Chemical Structure| 1832671-96-1 同义名 : -
CAS号 : 1832671-96-1
货号 : A1149116
分子式 : C16H15BrN2O5S
纯度 : 99%+
分子量 : 427.27
MDL号 : MFCD31813647
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 125 mg/mL(292.56 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
动物实验配方：
生物活性
靶点

  • BET

    BRD4 (1), Kd:82 nM
描述 Bromodomain and extra terminal domain (BET) family proteins, including BRD2, BRD3, BRD4, and BRDT, bind to acetylated lysines via their tandem domains (BD1 and BD2) to regulate gene transcription. These proteins have emerged as new therapeutic targets for human diseases and conditions, including cancers and inflammation. Y06036 is a potent BET bromodomain inhibitor which bounds to the BRD4(1) bromodomain with Kd values of 82 nM. The compound also potently inhibited cell growth, colony formation, and the expression of AR, AR regulated genes, and MYC in prostate cancer cell lines. In C4-2B CRPC xenograft mice, mice were treated with intraperitoneal injections of vehicle or Y06036 at a dose of 50 mg/kg 5 times per week. The efficacy data showed that Y06036 exhibited strong antitumor activities during the 25-day treatment period, with a tumor growth inhibition (TGI) of 70%. To evaluate cytotoxicity for various cell lines, Y06036 was evaluated in a wide range of cancer cell lines. Y06036 was potent in AR-negative prostate cancer cells DU145 with IC50 > 6 μΜ and PC-3 with IC50 > 3 μΜ. Besides, the breast cancer cells MCF-7 and Hs578T also appeared to be sensitive to Y06036 and IC50s are 1 and 2.5 μΜ. The studies still showed that Y06036 displayed moderate (2.5 - 5 μΜ) or weak (> 5 μΜ) inhibitory effects in the rest of cancer cell lines. Further more, Y06036 exhibited weak cytotoxicity in the normal lung fibroblast cell line HFL-1 with IC50 values of 18.2 μΜ and 15.9 μΜ[2].
作用机制 Y06036 binds to the BRD4(1) bromodomain and forms hydrogen bond interactions with the seventh solvent water molecule. Importantly, the 6-OCH3 of Y06036 occupied the position of the acetylated lysine (K5Ac) hydrophobic chain[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.34mL

0.47mL

0.23mL

11.70mL

2.34mL

1.17mL

23.40mL

4.68mL

2.34mL
参考文献

[1]Zhang M, Zhang Y, et al. Structure-Based Discovery and Optimization of Benzo[ d]isoxazole Derivatives as Potent and Selective BET Inhibitors for Potential Treatment of Castration-Resistant Prostate Cancer (CRPC). J Med Chem. 2018 Apr 12;61(7):3037-3058.

[2]Zhang M, Zhang Y, Song M, Xue X, Wang J, Wang C, Zhang C, Li C, Xiang Q, Zou L, Wu X, Wu C, Dong B, Xue W, Zhou Y, Chen H, Wu D, Ding K, Xu Y. Structure-Based Discovery and Optimization of Benzo[ d]isoxazole Derivatives as Potent and Selective BET Inhibitors for Potential Treatment of Castration-Resistant Prostate Cancer (CRPC). J Med Chem. 2018 Apr 12;61(7):3037-3058.