PF-543 hydrochloride

Research use only, not for human use.

PF-543 inhibits SphK1 with a K(i) of 3.6 nM, is sphingosine-competitive and is more than 100-fold selective for SphK1 over the SphK2 isoform.

PF-543 inhibits SphK1 with a K(i) of 3.6 nM, is sphingosine-competitive and is more than 100-fold selective for SphK1 over the SphK2 isoform.

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 C17-S1P formation in 1483 cells with an IC50 of 1.0 nM.SphK1 inhibition by PF-543 causes a dose-dependent depletion of the intracellular level of S1P with EC50 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 ?hoursResult: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 T1/2 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 hypertensionDosage:1 mg/kg Administration:Intraperitoneal injection; every second day; for 21 daysResult: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.

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GPCR/G Protein

S1P Receptor

SphK1

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1706522-79-3

502.1

C27H32ClNO4S

>98% (HPLC)

DMSO:≥90 mg/mL (136.83mM)

OC[C@@H]1N(CC2=CC=C(COC3=CC(CS(=O)(C4=CC=CC=C4)=O)=CC(C)=C3)C=C2)CCC1.[H]Cl

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(-20℃)

With Ice Pack

≥ 2 years