PF543

PF-543 is a small-molecule inhibitor developed as a potent and selective inhibitor of sphingosine kinase 1 (SphK1). It was developed by Pfizer and is used as a tool compound in sphingolipid signaling research. PF-543 is not approved for medical use and is intended for research purposes in laboratory settings.

Mechanism and selectivity: PF-543 inhibits SphK1, reducing the conversion of sphingosine to sphingosine-1-phosphate (S1P). This lowers cellular S1P levels and can shift the sphingolipid balance toward ceramide and sphingosine, which are associated with different effects on cell survival, proliferation, and apoptosis. The compound is reported to be highly selective for SphK1, with substantially weaker activity on SphK2, allowing researchers to probe isoform-specific roles in signaling pathways.

Applications: In vitro, PF-543 has been used in studies of cancer biology, inflammation, and neurobiology to investigate the contribution of SphK1 and S1P signaling to processes such as cell proliferation, migration, and cytokine production. Its use as a pharmacological probe helps delineate the distinct roles of SphK1 versus SphK2 in various cellular contexts. Data from in vivo studies are more limited, and when present, focus on pharmacology, bioavailability, and off-target considerations in animal models.

Availability and safety: As a research chemical, PF-543 is not available as an approved therapeutic and should be handled in accordance with standard laboratory safety and chemical-use guidelines.