PF-543 |
| Katalog-Nr.GC11917 |
PF-543 is a potent, selective, reversible, and sphingosine-competitive inhibitor of SphK1 with an IC50 value of 2nM and a Ki value of 3.6 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1415562-82-1
Sample solution is provided at 25 µL, 10mM.
PF-543 is a potent, selective, reversible, and sphingosine-competitive inhibitor of SphK1 with an IC50 value of 2nM and a Ki value of 3.6 nM[1]. SphK1 is a kinase that phosphorylates sphingosine to sphingosine-1-phosphate (S1P), which promotes cell growth, survival, and migration, and regulates lymphocyte trafficking. The selectivity of PF-543 for SPHK 1 is over 100 times that of SPHK 2[2]. PF-543 induces apoptosis, necrosis, and autophagy.
In vitro, PF-543 inhibits the formation of C17-S1P in 1483 cells, with an IC50 of 1.0 nM[1]; PF-543 inhibits SphK1 leading to a dose-dependent depletion of intracellular S1P levels, with an EC50 of 8.4 nM and an accompanying increase in intracellular sphingosine levels in 1483 cells[1]; PF-543 (10-1000 nM; 24h) treatment eliminates SK expression in PASM cells[1]. Treatment with 200 nM PF-543 for 1h decreased endogenous S1P levels by tenfold in 1483 cells, with a corresponding increase in sphingosine levels[2]. PF-543 (0.1-10 μM; 24 h) treatment of PASM cells induces caspase-3/7 activity[3].
In vivo, PF-543 (1 mg/kg; intraperitoneal injection; every other day; for 3 weeks) reduces right ventricular hypertrophy in female C57BL/6 J mice, decreases the expression of p53, increases the expression of the antioxidant nuclear factor Nrf-2, but has no effect on vascular remodeling[3]. When mice were initially treated with an intraperitoneal injection of 10 mg/kg or 30 mg/kg PF-543 for 24 h, the blood sample T1/2 was 1.2 h, which could induce a decrease in SK1 expression in the pulmonary vasculature[3].
References:
[1] Schnute M E et al. , Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1. Biochem J. 2012, 444(1): 79-88.
[2] 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.
[3] 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.
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Cell experiment [1]: |
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Cell lines |
1483 cells |
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Preparation method |
PF-543 modulates the levels of endogenous sphingosine and S1P. Lipids were extracted from 1483 cells treated for 1 h at 37℃ in medium lacking serum with a range of concentrations of PF-543(0.01, 0.1, 1, 10, 100, 1000nM). Lipids were quantified using MS |
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Reaction Conditions |
1 μM；1 h |
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Applications |
In 1483 cells pretreated for 1h with a range of concentrations of PF-543, PF-543 dose-dependently depleted the intracellular level of S1P with EC50 concentration of 8.4 nM and elevated the intracellular level of sphingosine. PF-543 showed no effect on the growth of several other cancer cell lines. PF-543 inhibited S1P formation in human whole blood (IC50=26.7 nM). |
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Animal experiment [2]: |
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Animal models |
Mouse hypoxic model of pulmonary hypertension |
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Preparation method |
Mice were placed into a hypobaric chamber and maintained at 550 mbar atmospheric pressure (~ 10% O2 concentration) for a period of 3 weeks. Every second day mice received an intraperitoneal injection of RB-005, PF-543 (10 mg/kg and 1 mg/kg, respectively) or vehicle (20% (2-Hydroxypropyl)-β-cyclodextrin in PBS). The chamber was depressurized and then repressurised in order to inject the mice . Mice were initially dosed (i.p.) with 10 mg/kg or 30 mg/kg of PF-543 for 24 h. |
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Dosage form |
i.p.; 10 mg/kg or 30 mg/kg; 24 h |
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Applications |
In a mouse hypoxic model of pulmonary hypertension, PF-543 showed no effect on vascular remodelling but reduced right ventricular hypertrophy. Administration of 10 mg/kg PF-543 for 24 h to mice decreased SK1 expression in pulmonary vessels. |
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References: [1] Schnute M E et al. , Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1. Biochem J. 2012, 444(1): 79-88. [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. |
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| Cas No. | 1415562-82-1 | SDF | |
| Chemical Name | [(2R)-1-[[4-[[3-(benzenesulfonylmethyl)-5-methylphenoxy]methyl]phenyl]methyl]pyrrolidin-2-yl]methanol | ||
| Canonical SMILES | CC1=CC(=CC(=C1)OCC2=CC=C(C=C2)CN3CCCC3CO)CS(=O)(=O)C4=CC=CC=C4 | ||
| Formula | C27H31NO4S | M.Wt | 465.6 |
| Löslichkeit | ≥ 23.3 mg/mL in DMSO, ≥ 51 mg/mL in EtOH with ultrasonic and warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1478 mL | 10.7388 mL | 21.4777 mL |
| 5 mM | 0.4296 mL | 2.1478 mL | 4.2955 mL |
| 10 mM | 0.2148 mL | 1.0739 mL | 2.1478 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
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Quality Control & SDS
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- Purity: >98.00%
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