PF 543 hydrochloride

Biological Activity

PF 543 hydrochloride is a potent and selective SphK1 inhibitor (IC₅₀ = 2 nM; K_i = 3.6 nM). Exhibits >100-fold selectivity for Sphk1 over Sphk2. Also exhibits >5,000 fold selectivity over S1P_1-5 receptors and 48 protein and lipid kinases. Inhibits growth and metastasis of several types of cancer cell including ovarian, colorectal and breast cancers, and suppresses HCT-116 tumor xenograft growth in mice. Antifibrotic and anti-inflammatory in a range of in vivo disease models. Also reduces sickling, hemolysis and inflammation in a transgenic mouse model of sickle cell disease.

Technical Data

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.

Additional Information

Background References

1. Discovery of a potent and selective sphingosine kinase 1 inhibitor through the molecular combination of chemotype-distinct screening hits
   Schnute et al.
   J.Med.Chem., 2017;60:2562
2. Targeting colorectal cancer cells by a novel sphingosine kinase 1 inhibitor PF-543.
   Ju et al.
   Biochem.Biophys.Res.Commun., 2016;470:728
3. Modulation of cellular S1P levels with a novel, potent and specific inhibitor of sphingosine kinase-1.
   Schnute et al.
   Biochem.J., 2012;444:79
4. Elevated sphingosine-1-phosphate promotes sickling and sickle cell disease progression.
   Zhang et al.
   J.Clin.Invest., 2014;124:2750
5. A chemical screen for modulators of mRNA translation identifies a distinct mechanism of toxicity for sphingosine kinase inhibitors
   A Corman, DC Kanellis, P Michalska, M Häggblad, V Lafarga, J Bartek, J Carreras-P, O Fernandez-
   PloS Biology, 2021;19(5):e3001263.

Product Datasheets