PROTAC BET degrader-2
目录号 : GC32980
PROTACBETdegrader-2是一种强效的溴域及末端外(BET)蛋白的降解剂，在RS4;11细胞中测得其对细胞生长的IC50值为9.6nM，并能实现肿瘤消退。
Cas No.:2093388-33-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
PROTAC BET degrader-2 is a highly potent degrader of Bromodomain and Extra-Terminal (BET) proteins with an IC50 value of 9.6 nM in cell growth inhibition in the RS4;11 cells and capable of achieving tumor regression.
PROTAC BET degrader-2 (compound 25) is a highly potent degrader of Bromodomain and Extra-Terminal (BET) proteins with an IC50 value of 9.6 nM in cell growth inhibition in the RS4;11 cells and capable of achieving tumor regression[1].
[1]. Zhou B, et al. Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression. J Med Chem. 2018 Jan 25;61(2):462-481.
| Cas No. | 2093388-33-9 | SDF | |
| Canonical SMILES | O=C(C1=NC(NC2=CC(C3CC3)=NN2CC)=C4C(NC5=C4C=C(OC)C(C6=C(C)ON=C6C)=C5)=N1)NCCCC7=CC=CC8=C7CN(C(CC9)C(NC9=O)=O)C8=O | ||
| 分子式 | C41H42N10O6 | 分子量 | 770.84 |
| 溶解度 | DMSO : 50 mg/mL (64.86 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 | 1.2973 mL | 6.4864 mL | 12.9729 mL |
| 5 mM | 0.2595 mL | 1.2973 mL | 2.5946 mL |
| 10 mM | 0.1297 mL | 0.6486 mL | 1.2973 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。
General Stepwise Approach to Optimize a TR-FRET Assay for Characterizing the BRD/PROTAC/CRBN Ternary Complex
ACS Pharmacol Transl Sci 2021 Feb 26;4(2):941-952.PMID:33860212DOI:PMC8033776
Proteolysis-targeting chimeras (PROTACs) degrade target proteins by engaging the ubiquitin-proteasome system. Assays detecting target-PROTAC-E3 ligase ternary complexes are critical for PROTAC development. Both time-resolved fluorescence energy transfer (TR-FRET) assays and amplified luminescent proximity homogeneous assays can characterize ternary complexes and assess PROTAC efficacy; stepwise optimization protocols for these assays are lacking. To identify assay conditions that can be applied to various targets and PROTACs, we used a stepwise approach to optimize a TR-FRET assay of BRD2(BD1)/PROTACs/CRBN ternary complexes. This assay is sensitive and specific and responds to the bivalent PROTACs dBET1, PROTAC BET Degrader-1, and PROTAC BET degrader-2 but not to non-PROTAC ligands of BRD2(BD1) or CRBN. The activity rank order of dBET1, PROTAC BET Degrader-1, and PROTAC BET degrader-2 in the TR-FRET assay corresponded with previously reported cell growth inhibition assays, indicating the effectiveness of our assay for predicting PROTAC cellular activity. The TR-FRET ternary complex formation assay for BRD2(BD1)/PROTAC/CRBN can be configured to characterize the binding activities of BRD2(BD1) and CRBN ligands with the same compound activity rank order as that of previously reported binary binding assays for individual targets but with the advantage of simultaneously assessing the ligand activities for both targets. Our assay is modular in nature, as BRD2(BD1) can be replaced with other BRDs and successfully detect ternary complexes without modifying other assay conditions. Therefore, the TR-FRET ternary complex assay for BRDs provides a general assay protocol for establishing assays for other targets and bivalent molecules.