iRucaparib-AP6
目录号 : GC39191
iRucaparib-AP6 是高效且特异的 PARP1 降解剂，基于 Rucaparib (PROTAC 的方法)。 iRucaparib-AP6 是一种 "非捕获性" PARP1 降解剂，可同时阻断 PARP1 的催化活性和支架作用。
Cas No.:2410557-00-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
iRucaparib-AP6 is a highly efficient and specific PARP1 degrader based on Rucaparib by using thePROTAC approach. iRucaparib-AP6, a non-trapping PARP1 degrader, blocks both the catalytic activity and scaffolding effects of PARP1[1].
[1]. Wang S, et al. Uncoupling of PARP1 trapping and inhibition using selective PARP1 degradation.Nat Chem Biol. 2019 Dec;15(12):1223-1231.
| Cas No. | 2410557-00-3 | SDF | |
| Canonical SMILES | O=C(NCC1)C2=CC(F)=CC3=C2C1=C(C4=CC=C(C=C4)CN(CCOCCOCCOCCOCCOCCOCCNC5=CC=CC(C(N6C7CCC(NC7=O)=O)=O)=C5C6=O)C)N3 | ||
| 分子式 | C46H55FN6O11 | 分子量 | 886.96 |
| 溶解度 | DMSO: 50 mg/mL (56.37 mM) | 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 | 1.1274 mL | 5.6372 mL | 11.2745 mL |
| 5 mM | 0.2255 mL | 1.1274 mL | 2.2549 mL |
| 10 mM | 0.1127 mL | 0.5637 mL | 1.1274 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。
Uncoupling of PARP1 trapping and inhibition using selective PARP1 degradation
Nat Chem Biol 2019 Dec;15(12):1223-1231.PMID:31659317DOI:PMC6864272
PARP1 inhibitors (PARPi) are known to kill tumor cells via two mechanisms (PARP1 catalytic inhibition and PARP1 trapping). The relative contribution of these two pathways in mediating the cytotoxicity of PARPi, however, is not well understood. Here we designed a series of small molecule PARP degraders. Treatment with one such compound iRucaparib-AP6 results in highly efficient and specific PARP1 degradation. iRucaparib-AP6 blocks the enzymatic activity of PARP1 in vitro, and PARP1-mediated poly-ADP-ribosylation signaling in intact cells. This strategy mimics PARP1 genetic depletion, which enables the pharmacological decoupling of PARP1 inhibition from PARP1 trapping. Finally, by depleting PARP1, iRucaparib-AP6 protects muscle cells and primary cardiomyocytes from DNA-damage-induced energy crisis and cell death. In summary, these compounds represent 'non-trapping' PARP1 degraders that block both the catalytic activity and scaffolding effects of PARP1, providing an ideal approach for the amelioration of the various pathological conditions caused by PARP1 hyperactivation.