生物活性
D159687 is a selective negative allosteric modulator (NAM) of PDE4D. D159687 induces a transient increase in CREB phosphorylation which peaked at 6 hours after treatment. D159687 causes optimal CREB phosphorylation at 1 μM.
In vivo, D159687 (0.05-5 mg/kg; oral daily for a week) shows a potential recruitment or enhancement of synaptic function with increased task difficulty in female Cynomolgus macaques.
化学数据
| 分子量 | 366.84 |
| 分子式 | C21H19ClN2O2 |
| CAS号 | 1155877-97-6 |
| 纯度 | >98% |
| 溶解性（25°C） | DMSO ≥ 90 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 | HT-22 cells |
| 方法 | cAMP concentrations were measured using the enzyme-linked immunosorbent assay (ELISA). On the day of treatment, the attached HT-22 cells were washed with warm phosphate buffer saline (PBS) and then incubated for 10 min with PBS supplemented with various concentrations of D159687 and further for 10 min with 10 nM isoproterenol in the system52. After incubation, PBS containing the drugs was removed and the plates were let dry roughly before 200 μl HCl (0.1 M) was added to each well to lyse the cells. Cell lysates were collected into Eppendorf tubes and centrifuged at 800 × g for 15 min. Supernatants were collected for immediate assay or stored frozen for assay later using the cAMP complete ELISA kit (Enzo Life Sciences, Farmingdale, NY) according to the assay protocol. |
| 浓度 | 0.1 and 1 μM |
| 处理时间 | - |
| 动物实验 |
|---|
| 动物模型 | Female Cynomolgus macaques (4-6 years; weights 2.39-3.6 Kg) |
| 配制 | prepared as solutions in a 0.5% (w/v) Poloxamer 188: 0.5% (w/v) HPMC: 0.4% Tween 80 vehicle at 5.0 mg/mL |
| 剂量 | 0.05, 0.5 and 5.0 mg/Kg |
| 给药处理 | PO gavage |
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 | 2.726 mL | 13.6299 mL | 27.2598 mL |
| 5 mM | 0.5452 mL | 2.726 mL | 5.452 mL |
| 10 mM | 0.2726 mL | 1.363 mL | 2.726 mL |
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