生物活性
Sephin1 (selective inhibitor of a holophosphatase) is a guanabez derivative that binds to and inhibits a regulatory subunit of the stress-induced protein phosphatase 1 (PPP1R15A), but not the constitutive PPP1R15B, and lacks ?2-adrenergic activity. Phosphorylation of eIF2α, α subunit of eukaryotic translation initiation factor 2, reduces protein synthesis and prevents the accumulation of misfolded protein in the endoplasmic reticulum (ER). PPP1R15A recruits the serine/threonine-protein phosphatase PP1 to dephosphorylate eIF2α, so inihbiting PPP1R15A activity prolongs the phosphorylation of eIF2α and aids in its prevention of the accumulation of misfolded protein.In vitroSephin1 protected cells from lethal protein misfolding and cytotoxic ER stress.In vivoSephin1 prevented two unrelated protein misfolding diseases in mice (Charchot-Marie-Tooth 1B and ALS).
化学数据
| 分子量 | 196.64 |
| 分子式 | C8H9ClN4 |
| CAS号 | 951441-04-6 |
| 纯度 | >98% |
| 溶解性（25°C） | DMSO: 20 mg/mL
clear |
| 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 | 5.0854 mL | 25.4272 mL | 50.8544 mL |
| 5 mM | 1.0171 mL | 5.0854 mL | 10.1709 mL |
| 10 mM | 0.5085 mL | 2.5427 mL | 5.0854 mL |
