Y06036
目录号 : GC33285Y06036 (Compound 6i) is a potent and selective inhibitor of BET with antitumor activity. Y06036 binds to the BRD4(1) bromodomain with Kd of 82 nM.
Cas No.:1832671-96-1
Sample solution is provided at 25 µL, 10mM.
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Y06036 (Compound 6i) is a potent and selective inhibitor of BET with antitumor activity. Y06036 binds to the BRD4(1) bromodomain with Kd of 82 nM.
[1] Maofeng Zhang, et al. J Med Chem. 2018 Apr 12;61(7):3037-3058.
Cas No. | 1832671-96-1 | SDF | |
Canonical SMILES | BrC1=CC(S(=O)(NC2=C(OC)C=C(ON=C3C)C3=C2)=O)=C(OC)C=C1 | ||
分子式 | C16H15BrN2O5S | 分子量 | 427.27 |
溶解度 | DMSO : 130 mg/mL (304.26 mM) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 2.3404 mL | 11.7022 mL | 23.4044 mL |
5 mM | 0.4681 mL | 2.3404 mL | 4.6809 mL |
10 mM | 0.234 mL | 1.1702 mL | 2.3404 mL |
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量) | ||||||||||
给药剂量 | mg/kg | 动物平均体重 | g | 每只动物给药体积 | ul | 动物数量 | 只 | |||
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% DMSO % % Tween 80 % saline | ||||||||||
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1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
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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.PMID:29566488DOI:10.1021/acs.jmedchem.8b00103
The bromodomain and extra-terminal (BET) family proteins have gained increasing interest as drug targets for treatment of castration-resistant prostate cancer (CRPC). Here, we describe the design, optimization, and evaluation of benzo[ d]isoxazole-containing compounds as potent BET bromodomain inhibitors. Cocrystal structures of the representative inhibitors in complex with BRD4(1) provided solid structural basis for compound optimization. The two most potent compounds, 6i (Y06036) and 7m (Y06137), bound to the BRD4(1) bromodomain with Kd values of 82 and 81 nM, respectively. They also exhibited high selectivity over other non-BET subfamily members. The compounds potently inhibited cell growth, colony formation, and the expression of AR, AR regulated genes, and MYC in prostate cancer cell lines. Compounds 6i and 7m also demonstrated therapeutic effects in a C4-2B CRPC xenograft tumor model in mice. These potent and selective BET inhibitors represent a new class of compounds for the development of potential therapeutics against CRPC.