DC-U4106
目录号 : GC67886DC-U4106 是一种 USP8 靶向抑制剂，其 Kd 值为 4.7 μM，IC50 值为 1.2 μM。DC-U4106 可作用于泛素化途径，促进 Erα 的降解。DC-U4106 可以抑制剂肿瘤细胞的生长，具有较小毒性，可用于乳腺癌研究。
Cas No.:2410534-62-0
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
DC-U4106 is a USP8 targeting inhibitor with the Kdvalue of 4.7 μM and the IC50 value of 1.2 μM. DC-U4106 can target the ubiquitin pathway and facilitate the degradation of Erα. DC-U4106 inhibits tumor growth with minimal toxicity and has the potential for the research of breast cancer[1].
DC-U4106 (1.2-45.2 μM) inhibits USP8 and USP2 with the IC50 values of 1.2 μM and 58.4 μM, respectively, and no activity in USP7[1].
DC-U4106 (0-7 μM, 24 hours) reduces mRNA levels of ERα and PR[1].
DC-U4106 (0-5 μM, 24 hours) can regulate the RTK pathway related proteins and the expression of ERα and PR proteins[1].
DC-U4106 (0-5 μM, 12 hours) can induce apoptosis and inhibit cell proliferation[1].
Western Blot Analysis[1]
| Cell Line: | USP8-positive cell line MCF-7 |
| Concentration: | 0-5 μM |
| Incubation Time: | 24 hours |
| Result: | Reduced the expression of EGFR, ErbB2, and ErbB3 proteins with increasing concentrations and caused degradation of ERα and PR proteins. |
RT-PCR[1]
| Cell Line: | USP8-positive cell line MCF-7 |
| Concentration: | 0-7 μM |
| Incubation Time: | 24 hours |
| Result: | Reduced mRNA levels of ERα and PR. |
Cell Proliferation Assay[1]
| Cell Line: | USP8-positive cell line MCF-7 |
| Concentration: | 0-5 μM |
| Incubation Time: | |
| Result: | Inhibited cell growth in a dose-dependent manner. |
Apoptosis Analysis[1]
| Cell Line: | USP8-positive cell line MCF-7 |
| Concentration: | 0-5 μM |
| Incubation Time: | 12 hours |
| Result: | Resulted in increasing in the proportion of apoptotic cells with increasing concentrations. |
DC-U4106 (intraperitoneal injection, 5 mg/kg or 20 mg/kg, every 2 days, 14 days) inhibits the proliferation of tumors and no significantly effects on body weight, organ morphology and structure in BALB/c nude mice[1].
| Animal Model: | BALB/c nude mice[1] |
| Dosage: | 5 mg/kg , 20 mg/kg |
| Administration: | Intraperitoneal injection, Every 2 days, 14 days |
| Result: | Inhibited tumor growth significantly at a concentration of 20 mg/kg. |
[1]. Yucheng Tian, et al. Discovery of Potent Small-Molecule USP8 Inhibitors for the Treatment of Breast Cancer through Regulating ERα Expression. J Med Chem. 2022 Jul 5.
| Cas No. | 2410534-62-0 | SDF | Download SDF |
| 分子式 | C29H27N5O5 | 分子量 | 525.56 |
| 溶解度 | 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 | 1.9027 mL | 9.5137 mL | 19.0273 mL |
| 5 mM | 0.3805 mL | 1.9027 mL | 3.8055 mL |
| 10 mM | 0.1903 mL | 0.9514 mL | 1.9027 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。
Discovery of Potent Small-Molecule USP8 Inhibitors for the Treatment of Breast Cancer through Regulating ERα Expression
J Med Chem 2022 Jul 14;65(13):8914-8932.PMID:35786929DOI:10.1021/acs.jmedchem.2c00013
Ubiquitin-specific protease 8 (USP8), belonging to the deubiquitinase family, has been implicated to be closely related to the occurrence of many malignant tumors, but only a few USP8-targeting inhibitors have been reported to date. In this study, we present virtual screening to discover novel hit candidates that inhibit the catalytic activity of USP8. Exploration of the structure-activity relationship led to the identification of compound DC-U4106, which binds to USP8 with a KD value of 4.7 μM and is selective over USP2 and USP7. Western blotting and immunoprecipitation showed that DC-U4106 could target the ubiquitin pathway and facilitate the degradation of ERα. In a xenograft tumor model, DC-U4106 also significantly inhibited tumor growth with minimal toxicity. Overall, our findings suggest that DC-U4106 is a promising drug candidate and targeting the USP8-ERα complex could be a new approach to treat ER-positive or drug-resistant breast cancer.