PF-543 (Citrate)

PF-543 Citrate (Sphingosine Kinase 1 Inhibitor II Citrate) is a potent, selective, reversible and sphingosine-competitive SPHK1 inhibitor with an IC50 of 2 nM and a Ki 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 IC50 of 26.7 nM. PF-543 Citrate induces apoptosis, necrosis, and autophagy[1][2][3].

[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.Mol Cell. 2020 Mar 19;77(6):1294-1306.e5. |Cancer Sci. 2020 Jul;111(7):2259-2274.|Cell Death Dis. 2024 Aug 1;15(8):552.|Hum Cell. 2020 Jan;33(1):57-66.|Inflammation. 2021 Dec;44(6):2170-2179.|Sci China Life Sci. 2021 May 27;1-21.|Sci Rep. 2020 Aug 14;10(1):13834.|FASEB J. 2024 Jan 31;38(2):e23417.