PF-543 (PF543) is a potent, specific, cell-permeant inhibitor of SphK1 with Ki of 3.6 nM, displays >100-fold selectivity over the SphK2 isoform.
PF-543 decreases the level of endogenous S1P 10-fold with a proportional increase in the level of sphingosine in 1483 head and neck carcinoma cells.
PF-543 reduces sickling, hemolysis, and inflammation in SCD Tg mice by reducing erythrocyte SPHK1 activity and S1P levels.
PF-543 induces apoptosis, necrosis, and autophagy in human head and neck SCC cells.
