PF-543 HCl 别名：PF-543 HCl; PF543 hydrochloride
PF-543 HCl 是一种有效的，选择性的，可逆和鞘氨醇竞争性的 SPHK1 抑制剂，IC50 为 2 nM，Ki 为 3.6 nM。PF-543 hydrochloride 对 SPHK1 的选择性是 SPHK2 的 100 倍以上。PF-543 HCl可诱导细胞凋亡、坏死和自噬。
CAS No.：1706522-79-3
化学性质/溶解性/储存
| 分子量 | 502.07 |
| 分子式 | C27H32ClNO4S |
| CAS号 | 1706522-79-3 |
| 溶解性 | DMSO ≥ 60 mg/mL |
| 储存条件 |
粉末型式 -20°C 3年；4°C 2年 溶于溶剂 -80°C 6个月；-20°C 1个月 |
| 运输方式 | 冰袋运输，根据产品的不同，可能会有相应调整。 |
生物活性
PF-543 hydrochloride is a potent, selective, reversible and sphingosine-competitive SPHK1 inhibitor with an IC50 of 2 nM and a Ki of 3.6 nM. PF-543 hydrochloride is >100-fold selectivity for SPHK1 over SPHK2. PF-543 was effective as a potent inhibitor of S1P formation in whole blood, indicating that the SphK1 isoform of sphingosine kinase is the major source of S1P in human blood. In the SphK1-overexpression 1483 head and neck carcinoma cells, PF-543 decreases the level of endogenous S1P 10-fold with a proportional increase in the level of sphingosine. PF-543 binds SphK1 reversibly (k off t1/2=8.5 min) and with high affinity and the binding constant (Kd) is 5 nM. PF543 had no effect on the proliferation and survival of 1483, A549, LN229, Jurkat, U937 and MCF-7 cells, despite a dramatic change in the cellular S1P/sphingosine ratio.
In vivo, administration of 10 mg/kg PF-543 for 24 h to mice induces a decrease in SK1 expression in pulmonary vessels.
实验参考
下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。
| 浓度/溶剂体积/质量 | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.9918 mL | 9.9588 mL | 19.9175 mL |
| 5 mM | 0.3984 mL | 1.9918 mL | 3.9835 mL |
| 10 mM | 0.1992 mL | 0.9959 mL | 1.9918 mL |
*吸湿的DMSO对产品的溶解度有显著影响，请使用新开封的DMSO；
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。
| 细胞系 | 1483, A549, LN229, Jurkat, U937, MCF-7 |
| 方法 | 1483 cells were cultured in DMEM/Ham’s F-12, A549 and LN229 cells were cultured in DMEM, Jurkat and U937 cells were cultured in RPMI 1640, and MCF-7 cells were cultured in Eagle’s MEM (minimal essential medium) with 0.01 mg/ml insulin. All media were supplemented with L-glutamine, Gentamicin and 10% FBS (or 0.5% FBS as indicated). The cells were grown in 96-well plates in 100 μl of medium with PF-543 or DMSO vehicle (0.01%) at 37 ◦C in an humidified incubator in the presence of 5% CO2. The cell growth and viability was measured using the CellTiter-Glo® Assay (Promega) by quantifying luminescence proportional to the amount of ATP present according to the manufacturer’s protocol. |
| 浓度 | ~1 μM |
| 处理时间 | 7 days |
* 上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
建议您制定动物给药及实验方案时，尽量参考已发表的相关实验文献（溶剂种类及配比众多，简单地溶解目的化合物，并不能解决动物给药依从性、体内生物利用度、组织分布等相关问题，未必能保证目的化合物在动物体内充分发挥生物学效用）。
体内实验的工作液，建议您现用现配，当天使用；如在配制过程中出现沉淀、析出现象，可以通过超声和（或）加热的方式助溶。
切勿一次性将产品全部溶解。
请在下面的计算器中，输入您的动物实验相关数据并点击计算，即可得到该实验的总需药量和工作液终浓度。
例如您给药剂量是10 mg/kg，平均每只动物的体重为20 g，每只动物的给药体积是100 μL，动物数量为20只，则该动物实验的总需药量为4 mg，工作液终浓度为2 mg/mL。
1：鉴于实验过程的损耗，建议您至少多配1-2只动物的量；
2：为该产品最终给药时的浓度。
| 动物模型 | Female C57BL/6 J mice (7-12 week-old) with hypoxic-induced pulmonary arterial hypertension |
| 配制 | dissolved in vehicle (20% (2-Hydroxypropyl)-β-cyclodextrin in phosphate buffered saline (PBS)) |
| 剂量 | 1 mg/kg |
| 给药处理 | Intraperitoneal injection; every second day; for 21 days |
* 上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
其他相关的SPHK产品
参考文献
