1415562-83-2
基本信息
(2R)-1-[[4-[[3-甲基-5-[(苯磺酰基)甲基]苯氧基]甲基]苯基]甲基]-2-吡咯烷甲醇柠檬酸盐
PWXXWUWKNPXSGW-VQIWEWKSSA-N
PF543 CITRATE
PF 543 CITRATE
Sphingosine Kinase 1 Inhibitor II Citrate
(2R)-1-[[4-[[3-Methyl-5-[(phenylsulfonyl)methyl]phenoxy]methyl]phenyl]methyl]-2-pyrrolidinemethanol 2-hydroxy-1,2,3-propanetricarboxylate
(2R)-1-[[4-[[3-Methyl-5-[(phenylsulfonyl)methyl]phenoxy]methyl]phenyl]methyl]-2-pyrrolidinemethanol 2-hydroxy-1,2,3-propanetricarboxylate (1:1)
物理化学性质
| 形态 | Powder |
| 颜色 | White to yellow |
常见问题列表
IC50: 2 nM (SPHK1); 26.7 nM (Sphingosine 1-phosphate (S1P))
Ki: 3.6 nM (SPHK1)
PF-543 (10-1000 nM; 24 hours; PASM cells) treatment abolishes SK1 expression at nM concentrations.
PF-543 (0.1-10 μM; 24 hours; PASM cells) treatment induces caspase-3/7 activity.
PF-543 inhibits C
17
-S1P formation in 1483 cells with an IC
50
of 1.0 nM.
SphK1 inhibition by PF-543 causes a dose-dependent depletion of the intracellular level of S1P with EC
50
concentration of 8.4 nM and a concomitant elevation of the intracellular level of sphingosine in 1483 cells. The level of endogenous S1P in 1483 cells after a 1 h treatment with 200 nM PF-543 is decreased 10-fold, producing a proportional increase in the level of sphingosine.
Western Blot Analysis
| Cell Line: | Human pulmonary arterial smooth muscle (PASM) cells |
| Concentration: | 10 nM, 100 nM, 1000 nM |
| Incubation Time: | 24 hours |
| Result: | Abolished SK1 expression at nM concentrations. |
Apoptosis Analysis
| Cell Line: | Human pulmonary arterial smooth muscle (PASM) cells |
| Concentration: | 0.1 μM, 1 μM, 10 μM |
| Incubation Time: | 24 hours |
| Result: | Induced caspase-3/7 activity in cultured human pulmonary smooth muscle cells. |
PF-543 (1 mg/kg; intraperitoneal injection; every second day; for 21 days; female C57BL/6 J mice) treatment has no effect on vascular remodelling but reduces right ventricular hypertrophy. The protection involves a reduction in the expression of p53 and an increase in the expression of anti-oxidant nuclear factor Nrf-2.
Mice are initially dosed (ip) with 10 mg/kg or 30 mg/kg of PF-543 for 24 h and the T
1/2
is 1.2 h in blood samples. Administration of 10 mg/kg PF-543 for 24 h to mice induces a decrease in SK1 expression in pulmonary vessels.
| Animal Model: | Female C57BL/6 J mice (7-12 week-old) with hypoxic-induced pulmonary arterial hypertension |
| Dosage: | 1 mg/kg |
| Administration: | Intraperitoneal injection; every second day; for 21 days |
| Result: | Reduced right ventricular hypertrophy. The protection involves a reduction in the expression of p53 (that promotes cardiomyocyte death) and an increase in the expression of anti-oxidant nuclear factor Nrf-2. |