BET bromodomain inhibitor
(Synonyms: BET抑制剂,CPI-0610; CPI0610; CPI 0610) 目录号 : GC16299
BET 溴结构域抑制剂是从专利 WO/2015/153871A2 化合物实施例 11 中提取的一种有效的 BET 抑制剂。
Cas No.:1380087-89-7
Sample solution is provided at 25 µL, 10mM.
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IC50: < 500 nM for BRD4
BET (bromodomain and extra-terminal) proteins regulate gene expression through their ability to bind to acetylated chromatin and subsequently activate RNA PolII-driven transcriptional elongation. The bromodomain (BRD) and extra-C terminal domain (BET) protein family consists of four members (BRD2, BRD3, BRD4 and BRDT).Small molecule BET inhibitors prevent binding of BET proteins to acetylated histones and inhibit transcriptional activation of BET target genes. BET inhibitors attenuate cell growth and survival in several hematologic cancer models, partially through the down-regulation of the critical oncogene, MYC. BET bromodomain inhibitor is a potent and selective inhibitor for BRD4.
In vitro: The most potent systhsized ompound presented is BET bromodomain inhibitor, which shows activity with IC50 < 500 nM against BRD4 [1].
In vivo: BET bromodomain inhibitor shows activity in vivo at < 10 mg/kg against BRD4 in rat [1].
Clinical trial: Up to now, BET bromodomain inhibitor is still in the preclinical development stage.
Reference:
[1] Garnier JM, Sharp PP, Burns CJ. BET bromodomain inhibitors: a patent review. Expert Opin Ther Pat. 2014 Feb;24(2):185-99.
| Cell experiment [1]: | |
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Cell lines |
Primary Multiple Myeloma cell lines |
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Preparation method |
The solubility of this compound in DMSO is >18.3mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
2 μM at 72 h |
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Applications |
CPI-0610 treatment resulted in 40% decrease in viability in primary cells isolated from a newly diagnosed patient and caused 50% cell death in primary cells isolated from a relapsed disease patient. |
| Animal experiment [1]: | |
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Animal models |
Multiple Myeloma xenograft CB17-SCID mouse model |
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Dosage form |
subcutaneous injections, 10 mg/kg, twice a day for 38 days |
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Application |
Mice treated with CPI-0610 showed a significant delay in tumor growth, and the median overall survival of CPI-0610 treated animals was significantly prolonged. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Siu KT, Ramachandran J, Yee AJ, et al. Preclinical activity of CPI-0610, a novel small-molecule bromodomain and extra-terminal protein inhibitor in the therapy of multiple myeloma. Leukemia. 2017 Jan 3. | |
| Cas No. | 1380087-89-7 | SDF | |
| 别名 | BET抑制剂,CPI-0610; CPI0610; CPI 0610 | ||
| 化学名 | 2-((4S)-6-(4-chlorophenyl)-1-methyl-4H-benzo[c]isoxazolo[4,5-e]azepin-4-yl)acetimidic acid | ||
| Canonical SMILES | CC1=NOC2=C1C3=CC=CC=C3C(C4=CC=C(Cl)C=C4)=N[C@@]2([H])CC(O)=N | ||
| 分子式 | C20H16ClN3O2 | 分子量 | 365.81 |
| 溶解度 | ≥ 18.3mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7337 mL | 13.6683 mL | 27.3366 mL |
| 5 mM | 0.5467 mL | 2.7337 mL | 5.4673 mL |
| 10 mM | 0.2734 mL | 1.3668 mL | 2.7337 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet