PF-543 Citrate (Sphingosine Kinase 1 Inhibitor II Citrate) is a potent, selective, reversible and sphingosine-competitive SPHK1 inhibitor with an IC 50 of 2 nM and a K i of 3.6 nM. PF-543 Citrate is >100-fold selectivity for SPHK1 over SPHK2 . PF-543 Citr
Storage Temp
Store at 2-8°C,Desiccated
Shipped In
Wet ice
Product Description
PF-543 Citrate (Sphingosine Kinase 1 Inhibitor II Citrate) is a potent, selective, reversible and sphingosine-competitive SPHK1 inhibitor with an IC 50 of 2 nM and a K i of 3.6 nM. PF-543 Citrate is >100-fold selectivity for SPHK1 over SPHK2 . PF-543 Citrate is an effective potent inhibitor of sphingosine 1-phosphate (S1P) formation in whole blood with an IC 50 of 26.7 nM. PF-543 Citrate induces apoptosis , necrosis, and autophagy
In Vitro
PF-543 (10-1000 nM; 24?hours; PASM cells) treatment abolishes SK1 expression at nM concentrations. ?\nPF-543 (0.1-10 μM; 24 hours; PASM cells) treatment induces caspase-3/7 activity. ?\nPF-543 inhibits C 17 -S1P formation in 1483 cells with an IC 50 of 1.0 nM. ?\nSphK1 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell 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 AnalysisCell 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.
In Vivo
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. ?\nMice 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Female C57BL/6 J mice (7-12 week-old) with hypoxic-induced pulmonary arterial hypertensionDosage: 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.
