PF-543 (Citrate)
PF-543 (Citrate) Basic information
- Product Name:
- PF-543 (Citrate)
- Synonyms:
-
- PF-543 (Citrate)
- (2R)-1-[[4-[[3-Methyl-5-[(phenylsulfonyl)methyl]phenoxy]methyl]phenyl]methyl]-2-pyrrolidinemethanol 2-hydroxy-1,2,3-propanetricarboxylate (1:1)
- (2R)-1-[[4-[[3-Methyl-5-[(phenylsulfonyl)methyl]phenoxy]methyl]phenyl]methyl]-2-pyrrolidinemethanol 2-hydroxy-1,2,3-propanetricarboxylate
- PWXXWUWKNPXSGW-VQIWEWKSSA-N
- PF543 CITRATE; PF 543 CITRATE
- Sphingosine Kinase 1 Inhibitor II Citrate
- CAS:
- 1415562-83-2
- MF:
- C33H39NO11S
- MW:
- 657.73
- Mol File:
- 1415562-83-2.mol
PF-543 (Citrate) Chemical Properties
- form
- Powder
- color
- White to yellow
PF-543 (Citrate) Usage And Synthesis
Uses
PF-543 Citrate (Sphingosine Kinase 1 Inhibitor II Citrate) is a potent, selective, reversible and sphingosine-competitive SPHK1 inhibitor with an IC50 of 2 nM and a Ki 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 IC50 of 26.7 nM. PF-543 Citrate induces apoptosis, necrosis, and autophagy[1][2][3].
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[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[2].
| Animal Model: | Female C57BL/6 J mice (7-12 week-old) with hypoxic-induced pulmonary arterial hypertension[2] |
| Dosage: | 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. |
IC 50
SphK1
References
[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. DOI:10.1042/BJ20111929
[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. DOI:10.1016/j.cellsig.2016.03.014
[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. DOI:10.1038/cddiscovery.2017.47
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