PF-543 hydrochloride  (Synonyms: Sphingosine Kinase 1 Inhibitor II hydrochloride)

PF-543 hydrochloride (Sphingosine Kinase 1 Inhibitor II hydrochloride) is a potent, selective, reversible and sphingosine-competitive SPHK1 inhibitor with an IC₅₀ of 2 nM and a K_i of 3.6 nM. PF-543 hydrochloride is >100-fold selectivity for SPHK1 over SPHK2. PF-543 hydrochloride is an effective potent inhibitor of sphingosine 1-phosphate (S1P) formation in whole blood with an IC₅₀ of 26.7 nM. PF-543 hydrochloride induces apoptosis, necrosis, and autophagy^[1][2][3].

IC50: 2 nM (SPHK1); 26.7 nM (Sphingosine 1-phosphate (S1P))^[1]
Ki: 3.6 nM (SPHK1)^[1]

PF-543 (10-1000 nM; 24 hours; PASM cells) treatment abolishes SK1 expression at nM concentrations^[2].
PF-543 (0.1-10 μM; 24 hours; PASM cells) treatment induces caspase-3/7 activity^[2].
PF-543 inhibits C₁₇-S1P formation in 1483 cells with an IC₅₀ of 1.0 nM^[1].
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^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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^[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^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

502.07

C₂₇H₃₂ClNO₄S

1706522-79-3

[H]Cl.O=S(C1=CC=CC=C1)(CC2=CC(C)=CC(OCC3=CC=C(CN4[C@@H](CO)CCC4)C=C3)=C2)=O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Schnute ME, et al. Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1. Biochem J. 2012 May 15;444(1):79-88.  [Content Brief]

  [2]. MacRitchie N, et al. Effect of the sphingosine kinase 1 selective inhibitor, PF-543 on arterial and cardiac remodelling in a hypoxic model of pulmonary arterial hypertension. Cell Signal. 2016 Aug;28(8):946-55.  [Content Brief]

  [3]. Hamada M, et al. Induction of autophagy by sphingosine kinase 1 inhibitor PF-543 in head and neck squamous cell carcinoma cells. Cell Death Discov. 2017 Aug 14;3:17047.  [Content Brief]