PF-543 hydrochloride

SKU: orb1218649

Description

PF-543 inhibits SphK1 with a K(i) of 3.6 nM, is sphingosine-competitive and is more than 100-fold selective for SphK1 over the SphK2 isoform.

Key Properties

• CAS Number: 1706522-79-3
• MW: 502.1
• Purity: >98% (HPLC)
• Formula: C₂₇H₃₂ClNO₄S
• SMILES: OC[C@@H]1N(CC2=CC=C(COC3=CC(CS(=O)(C4=CC=CC=C4)=O)=CC(C)=C3)C=C2)CCC1.[H]Cl
• Target: S1P Receptor
• Solubility: DMSO:≥90 mg/mL (136.83mM)

Bioactivity

• 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.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. Animal model: Female C57BL/6 J mice (7-12 week-old) with hypoxic-induced pulmonary arterial hypertension. 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.
• In Vitro:
  PF-543 (10-1000 nM; 24 hours; PASM cells) treatment abolishes SK1 expression at nM concentrations. PF-543 (0.1-10 μM; 24 hours; PASM cells) treatment induces caspase-3/7 activity. PF-543 inhibits C17-S1P formation in 1483 cells with an IC50 of 1.0 nM. 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. Western blot analysis. 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. 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

S1P Receptor