PF-543 Citrate

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. ? 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. 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. ? 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. 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. IC50& Target:SphK1

No numbering system information yet

No physical and chemical property information yet

No safety information yet

No production method and use information yet

No upstream information yet

No downstream information yet

No related product information yet