dBET6
目录号 : GC32719
A PROTAC that drives BRD4 degradation
Cas No.:1950634-92-0
Sample solution is provided at 25 µL, 10mM.
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dBET6 is a hybrid compound that drives the selective proteasomal degradation of bromodomain-containing protein 4 (BRD4).1 It is characterized as a proteolysis-targeting chimera (PROTAC) and contains JQ1, which binds bromo- and extra-terminal (BET) proteins, linked to thalidomide, a ligand for the E3 ubiquitin ligase cereblon.2 dBET6 binds to BRD4 (IC50 = 14 nM) and induces its degradation when used at a concentration of 100 nM, leading to a global inhibition of transcription in MOLT-4 T cell acute lymphoblastic leukemia (T-ALL) cells.1 It also reduces leukemic burden in a MOLT-4 T-ALL mouse xenograft model when administered at a dose of 7.5 mg/kg twice per day.
1.Winter, G.E., Mayer, A., Buckley, D.L., et al.BET bromodomain proteins function as master transcription elongation factors independent of CDK9 recruitmentMol. Cell67(1)5-18(2017) 2.Goracci, L., Desantis, J., Valeri, A., et al.Understanding the metabolism of proteolysis targeting chimeras (PROTACs): The next step toward pharmaceutical applicationsJ. Med. Chem.63(20)11615-11638(2020)
Animal experiment: | Mice[1]MOLT4 human T-ALL cells are intravenously injected into NSG mice (2×106 cells/mouse). Luminescence is utilized to monitor engraftment (evident at day 6), at which point mice are randomized into three cohorts that receive dBET6 (7.5 mg/kg BID, n = 8), JQ1 (20 mg/kg QD, n = 9) or vehicle (captisol, n = 9) treatment for 14 days. Survival of all three cohorts is subsequently monitored using hind limb paralysis caused by high femoral leukemic burden as a defined endpoint. SUPT11 human T-ALL cells (mCherry+ and Luciferase+) are intravenously injected into NSG mice (2.52×106 cells/mouse). Luminescence is used to monitor successful engraftment, occurring 10 days after injection. At this point, animals are randomized into three cohorts that receive dBET6 (7.5 mg/kg BID, n = 7), JQ1 (7.5 mg/kg BID, n = 7) or vehicle (captisol, n = 7) treatment for 18 days. Treatment burden is assessed via total body luminescence imaging as well as by bone marrow infiltration by mCherry+ T-ALL cells[1]. |
References: [1]. Winter GE, et al. BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment. Mol Cell. 2017 Jul 6;67(1):5-18.e19. | |
| Cas No. | 1950634-92-0 | SDF | |
| Canonical SMILES | O=C(NCCCCCCCCNC(COC1=CC=CC(C(N2C(CC3)C(NC3=O)=O)=O)=C1C2=O)=O)C[C@H]4C5=NN=C(C)N5C6=C(C(C)=C(C)S6)C(C7=CC=C(Cl)C=C7)=N4 | ||
| 分子式 | C42H45ClN8O7S | 分子量 | 841.37 |
| 溶解度 | DMSO : ≥ 100 mg/mL (118.85 mM);Water : < 0.1 mg/mL (insoluble) | 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 | 1.1885 mL | 5.9427 mL | 11.8854 mL |
| 5 mM | 0.2377 mL | 1.1885 mL | 2.3771 mL |
| 10 mM | 0.1189 mL | 0.5943 mL | 1.1885 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