PF-543

SKU: orb1689183

Description

PF-543 is a potent and selective sphingosine-competitive inhibitor of Sphingosine Kinase 1 (SphK1), exhibiting an IC50 of 2.0 nM and a Ki of 3.6 nM. This cell-permeable compound is a valuable research tool for investigating the role of SphK1 and sphingosine-1-phosphate signaling in cancer, inflammation, and fibrosis in both cellular and animal models.

Research Area

Cell Biology, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 1415562-82-1
• MW: 465.6
• Purity: 99.29% (May vary between batches)
• Formula: C₂₇H₃₁NO₄S
• SMILES: Cc1cc(CS(=O)(=O)c2ccccc2)cc(OCc2ccc(CN3CCC[C@@H]3CO)cc2)c1
• Target: Apoptosis,Autophagy,S1P Receptor,LPL Receptor
• Solubility: H2O:<1 mg/mL;10% DMSO+90% Corn Oil:5 mg/mL (10.74 mM);DMSO:93 mg/mL (199.74 mM);Ethanol:93 mg/mL (199.74 mM)

Bioactivity

• Target IC50:
  SPHK1:2.0 nM|SPHK1:3.6 nM(Ki)
• In Vivo:
  Administration of the potent sphingosine kinase 1 inhibitor, PF-543 in a mouse hypoxic model of pulmonary hypertension has no effect on vascular remodelling but reduces right ventricular hypertrophy. Administration of 10 mg/kg PF-543 for 24 h to mice induces a decrease in SK1 expression in pulmonary vessels.
• In Vitro:
  PF543 is a cell-permeable hydroxyl methylpyrrolidine compound that inhibits SphK-1/SphK1-catalyzed sphingosine phosphorylation in a reversible and sphingosine-competitive manner, exhibiting no affinity toward S1P receptors and much reduced inhibitory activity against Sphk2 (6.8% inhibition at 10 μM) or 46 other lipid and portein kinases (IC50 >10 μM). In the SphK1-overexpression 1483 head and neck carcinoma cells, PF-543 decreases the level of endogenous S1P 10-fold with a proportional increase in the level of sphingosine. PF-543 binds SphK1 reversibly (k off t1/2=8.5 min) and with high affinity and the binding constant (Kd) is 5 nM. PF543 had no effect on the proliferation and survival of 1483, A549, LN229, Jurkat, U937 and MCF-7 cells, despite a dramatic change in the cellular S1P/sphingosine ratio. PF-543 is effective as a potent inhibitor of S1P formation in whole blood, indicating that the SphK1 isoform of sphingosine kinase is the major source of S1P in human blood.
• Cell Research:
  CellTiter-Glo Assay (Only for Reference)

Storage & Handling

• Storage: store at low temperature | Pure form: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Lysophospholipid Receptor, PAH, necrosis, inhibit, LPL, LPLReceptor, LPL Receptor, Nrf-2, Inhibitor, Autophagy, anti-cancer, anti-inflammatory, Apoptosis, caspase-3/7, SphK, Sphingosine kinase, Sphingosine Kinase 1 Inhibitor II, sphingosine-competitive, SphK1, S1P Receptor, S1PReceptor, S1P, PF-543, PF543, PF 543, SK1

Compound Identifiers

PubChem CID

66577038