CP5V
目录号 : GC62181
CP5V 是一种 PROTAC，通过连接 Cdc20 与 VHL/VBC 复合物进行泛素化和蛋白酶体降解，特异性地降解 Cdc20。CP5V 诱导有丝分裂抑制及抑制癌细胞增殖。
Cas No.:2509359-75-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
CP5V is a PROTAC, which specifically degrades Cdc20 by linking Cdc20 to the VHL/VBC complex for ubiquitination followed by proteasomal degradation. CP5V induces mitotic inhibition and suppresses cancer cell proliferation[1].
CP5V comprises a Cdc20 ligand and VHL binding moiety bridged by a PEG5 linker that induces Cdc20 degradation. CP5V induces degradation of Cdc20 leading to significant inhibition of breast cancer cell proliferation and resensitization of Taxol-resistant cell lines[1].CP5V profoundly degrades Cdc20 in both MCF7 and MDA-MB-231 cells with DC50 being approximately 1.6 μM[1].
[1]. Chi JJ, et al. A novel strategy to block mitotic progression for targeted therapy. EBioMedicine. 2019 Oct 25. pii: S2352-3964(19)30677-2.
| Cas No. | 2509359-75-3 | SDF | |
| 分子式 | C46H66Cl3N9O12S | 分子量 | 1075.49 |
| 溶解度 | DMSO : 150 mg/mL (139.47 mM; Need ultrasonic) | 储存条件 | Store at -20°C, stored under nitrogen |
| 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 | 0.9298 mL | 4.649 mL | 9.2981 mL |
| 5 mM | 0.186 mL | 0.9298 mL | 1.8596 mL |
| 10 mM | 0.093 mL | 0.4649 mL | 0.9298 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。
A novel strategy to block mitotic progression for targeted therapy
EBioMedicine 2019 Nov;49:40-54.PMID:31669221DOI:PMC6945239
Background: Blockade of mitotic progression is an ideal approach to induce mitotic catastrophe that suppresses cancer cell expansion. Cdc20 is a critical mitotic factor governing anaphase initiation and the exit from mitosis through recruiting substrates to APC/C for degradation. Results from recent TCGA (The Cancer Genome Atlas) and pathological studies have demonstrated a pivotal oncogenic role for Cdc20-APC/C in tumor progression as well as drug resistance. Thus, deprivation of the mitotic role for Cdc20-APC/C by either inhibition of Cdc20-APC/C activity or elimination of Cdc20 protein via induced protein degradation emerges as an effective therapeutic strategy to control cancer. Methods: We designed a proteolysis targeting chimera, called CP5V, which comprises a Cdc20 ligand and VHL binding moiety bridged by a PEG5 linker that induces Cdc20 degradation. We characterized the effect of CP5V in destroying Cdc20, arresting mitosis, and inhibiting tumor progression by measuring protein degradation, 3D structure dynamics, cell cycle control, tumor cell killing and tumor inhibition using human breast cancer xenograft mouse model. Findings: Results from our study demonstrate that CP5V can specifically degrade Cdc20 by linking Cdc20 to the VHL/VBC complex for ubiquitination followed by proteasomal degradation. Induced degradation of Cdc20 by CP5V leads to significant inhibition of breast cancer cell proliferation and resensitization of Taxol-resistant cell lines. Results based on a human breast cancer xenograft mouse model show a significant role for CP5V in suppressing breast tumor progression. Interpretation: CP5V-mediated degradation of Cdc20 could be an effective therapeutic strategy for anti-mitotic therapy.