生物活性
Misfolded proteins accumulate in many neurodegenerative diseases, including huntingtin in Huntington′s disease and alpha-synuclein in Parkinson′s disease. The disease-causing proteins can take various conformations and are prone to aggregate and form larger cytoplasmic or nuclear inclusions. CPNQ (B2) was identified as a compound that promotes inclusion formation in cellular models of both Huntington′s disease and Parkinson′s disease. Despite the aggregate-forming specifics the compound prevents huntingtin-mediated proteasome dysfunction and reduces alpha-synuclein-mediated toxicity. These results demonstrate that compounds that increase inclusion formation may actually lessen cellular pathology in both Huntington′s and Parkinson′s diseases, suggesting a therapeutic approach for neurodegenerative diseases caused by protein misfolding. The ability of B2 to prevent toxicity, despite increasing inclusions, suggests that inclusions are beneficial rather than toxic, which will be further explored as the molecular target and mechanism. CPNQ (B2) is a desirable tool for both Huntington′s and Parkinson′s research.
化学数据
分子量 | 396.83 |
分子式 | C20H17ClN4O3 |
CAS号 | 115687-05-3 |
纯度 | >98% |
溶解性(25°C) | N/A |
储存和运输条件 | 固体粉末: -20°C 冷藏长期储存 常温运输及临时存放 |
不同实验动物依据体表面积的等效剂量转换表(数据来源于FDA指南)
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 |
重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km系数 | 3 | 6 | 12 | 8 | 5 | 20 |
动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
动物 A的Km系数 |
例如,依据体表面积折算法,将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量,需要将20 mg/kg 乘以小鼠的Km系数(3),再除以大鼠的Km系数(6),得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
以下数据基于产品分子量,对于特殊产品,请参照COA中的储备液配制条件和说明进行操作。
Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
---|
1 mM | 2.52 mL | 12.5999 mL | 25.1997 mL |
5 mM | 0.504 mL | 2.52 mL | 5.0399 mL |
10 mM | 0.252 mL | 1.26 mL | 2.52 mL |