| Identification | Back Directory | [Name]
PF-543 (Citrate) | [CAS]
1415562-83-2 | [Synonyms]
PF-543 (Citrate)
PWXXWUWKNPXSGW-VQIWEWKSSA-N
PF543 CITRATE; PF 543 CITRATE
Sphingosine Kinase 1 Inhibitor II Citrate
(2R)-1-[[4-[[3-Methyl-5-[(phenylsulfonyl)methyl]phenoxy]methyl]phenyl]methyl]-2-pyrrolidinemethanol 2-hydroxy-1,2,3-propanetricarboxylate
(2R)-1-[[4-[[3-Methyl-5-[(phenylsulfonyl)methyl]phenoxy]methyl]phenyl]methyl]-2-pyrrolidinemethanol 2-hydroxy-1,2,3-propanetricarboxylate (1:1) | [Molecular Formula]
C33H39NO11S | [MDL Number]
MFCD23098795 | [MOL File]
1415562-83-2.mol | [Molecular Weight]
657.728 |
| Hazard Information | Back Directory | [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].
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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.
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| [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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| Company Name: |
SPIRO PHARMA
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| Tel: |
|
| Website: |
www.spiropharma.com.cn |
| Company Name: |
Musechem
|
| Tel: |
+1-800-259-7612 |
| Website: |
www.musechem.com |
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