生物活性
PF-4800567是一种选择性的、ATP竞争性的酪蛋白激酶1ε抑制剂，对CK1ε和CK1δ的IC50值分别为32和711 nM。酪蛋白激酶1 (CK1epsilon)和酪蛋白激酶1delta (CK1delta)是密切相关的Ser-Thr蛋白激酶，它们作为关键的时钟调节因子，哺乳动物的突变极大地改变了昼夜节律。PF-4800567对CK1ε的效力是CK1δ的22倍。PF-4800567完全阻断ck1epsilon介导的PER3核定位和PER2降解。
化学数据
| 分子量 | 359.81 |
| 分子式 | C17H18ClN5O2 |
| CAS号 | 1188296-52-7 |
| 纯度 | >98% |
| 溶解性（25°C） | DMSO ≥30 mg/mL |
| 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 |
实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）
| 细胞实验 |
|---|
| 细胞系 | COS-7 cells |
| 方法 | Nuclear Translocation.
CK1ε- and CK1δ-dependent PER3 nuclear translocation was run as described previously for CK1ε (Badura et al., 2007), with alterations as indicated below. CK1δ-dependent PER3 nuclear translocation was performed with human full-length CKIδ-pcDNA4/HisA cotransfected into COS-7 cells with the GFP-tagged murine PER3. The sensitivity of the assay was increased by incorporating an anti-GFP antibody-staining step. After the plates were fixed with 4% paraformaldehyde and washed in PBS, cells were blocked and permeabilized in PBS with 4% goat serum and 0.1% Triton X-100 for 1 h at room temperature. Blocking buffer was then replaced with a polyclonal anti-GFP antibody (Invitrogen), diluted 1:1000 in blocking buffer, and incubated for 2 h. After three washes in PBS, goat anti-rabbit Alexa Fluor 488 secondary antibody (Invitrogen), diluted 1:1000 in Hoechst staining solution, was added and incubated for 1 h before three final washes in PBS. |
| 浓度 | 0, 0.01, 0.1, 1, 10μM |
| 处理时间 | 1~2 hr |
| 动物实验 |
|---|
| 动物模型 | C57BL/6J mice |
| 配制 | 20% hydroxypropyl β-cyclodextrin |
| 剂量 | 100 mg/kg daily for 3 days |
| 给药处理 | s.c. |
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 | 2.7792 mL | 13.8962 mL | 27.7924 mL |
| 5 mM | 0.5558 mL | 2.7792 mL | 5.5585 mL |
| 10 mM | 0.2779 mL | 1.3896 mL | 2.7792 mL |
m.cnreagent.com