[CAS NO. 1415562-83-2] PF-543Citrate
PRODUCTS SPECIFICATIONS [1415562-83-2]
DESCRIPTION [1415562-83-2]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 657.73 |
| Molecular Formula | C33H39NO11S |
| SMILES | OC(C(O)=O)(CC(O)=O)CC(O)=O.O=S(C1=CC=CC=C1)(CC2=CC(C)=CC(OCC3=CC=C(CN4[C@@H](CO)CCC4)C=C3)=C2)=O |
6 Publications Citing Use of MCE
Summary
PF-543 Citrate (Sphingosine Kinase 1 Inhibitor II Citrate) is a potent, selective, reversible and sphingosine-competitive SPHK1 inhibitor with an IC 50 of 2 nM and a K i 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 IC 50 of 26.7 nM. PF-543 Citrate induces apoptosis , necrosis, and autophagy [1] [2] [3] .
IC50 & Target
In Vitro
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 C
17
-S1P formation in 1483 cells with an IC
50
of 1.0 nM
[1]
.
SphK1 inhibition by PF-543 causes a dose-dependent depletion of the intracellular level of S1P with EC
50
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis [2]
| Cell Line: | Human pulmonary arterial smooth muscle (PASM) cells |
| Concentration: | 10 nM, 100 nM, 1000 nM |
| Incubation Time: | 24 hours |
| Result: | Abolished SK1 expression at nM concentrations. |
Apoptosis Analysis [2]
| 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. |
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 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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : ≥ 100 mg/mL ( 152.04 mM )
H 2 O : 50 mg/mL ( 76.02 mM ; Need ultrasonic)
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.5204 mL | 7.6019 mL | 15.2038 mL |
| 5 mM | 0.3041 mL | 1.5204 mL | 3.0408 mL |
| 10 mM | 0.1520 mL | 0.7602 mL | 1.5204 mL |
-
1.
Add each solvent one by one: PBS
Solubility: 100 mg/mL (152.04 mM); Clear solution; Need ultrasonic
-
2.
-
3.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 2.5 mg/mL (3.80 mM); Clear solution
-
4.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (3.80 mM); Clear solution
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.
- [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.
- [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.