T0467
目录号 : GC63669
T0467 以 PINK1 依赖的方式激活线粒体 parkin 易位。T0467 不诱导多巴胺能神经元中 PINK1 的线粒体聚集。T0467 是一种潜在的PINK1-Parkin 信号激活化合物，可用于帕金森病及相关疾病的研究。
Cas No.:859518-94-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
T0467 activates parkin mitochondrial translocation in a PINK1-dependent manner in vitro. T0467 do not induce mitochondrial accumulation of PINK1in dopaminergic neurons. T0467 is a potential compound for PINK1-Parkin signaling activation, and can be used for parkinson’s disease and related disorders research[1].
T0467 (2.5-20 μM; 3 hours) stimulates the mitochondrial translocation of GFP-Parkinover 12 μM in HeLa/GFP-Parkin cells[1]. When HeLa/GFP-Parkin cells are treated with 20 μM T0467 for 3 h, GTP-Parkin is translocated to the mitochondria in approximately 21% of cells[1].T0467 does not show obvious toxicity in Drosophila at concentrations Drosophila larval muscles[1].
[1]. Kahori Shiba-Fukushima, et al. A Cell-Based High-Throughput Screening Identified Two Compounds that Enhance PINK1-Parkin Signaling. iScience. 2020 May 22;23(5):101048.
| Cas No. | 859518-94-8 | SDF | |
| 分子式 | C24H26F3N5 | 分子量 | 441.49 |
| 溶解度 | DMSO : 33.33 mg/mL (75.49 mM; Need ultrasonic) | 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 | 2.2651 mL | 11.3253 mL | 22.6506 mL |
| 5 mM | 0.453 mL | 2.2651 mL | 4.5301 mL |
| 10 mM | 0.2265 mL | 1.1325 mL | 2.2651 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 Cell-Based High-Throughput Screening Identified Two Compounds that Enhance PINK1-Parkin Signaling
iScience 2020 May 22;23(5):101048.PMID:32335362DOI:PMC7183160
Early-onset Parkinson's disease-associated PINK1-Parkin signaling maintains mitochondrial health. Therapeutic approaches for enhancing PINK1-Parkin signaling present a potential strategy for treating various diseases caused by mitochondrial dysfunction. We report two chemical enhancers of PINK1-Parkin signaling, identified using a robust cell-based high-throughput screening system. These small molecules, T0466 and T0467, activate Parkin mitochondrial translocation in dopaminergic neurons and myoblasts at low doses that do not induce mitochondrial accumulation of PINK1. Moreover, both compounds reduce unfolded mitochondrial protein levels, presumably through enhanced PINK1-Parkin signaling. These molecules also mitigate the locomotion defect, reduced ATP production, and disturbed mitochondrial Ca2+ response in the muscles along with the mitochondrial aggregation in dopaminergic neurons through reduced PINK1 activity in Drosophila. Our results suggested that T0466 and T0467 may hold promise as therapeutic reagents in Parkinson's disease and related disorders.