Uses
(2R)-1-[[4-[[3-Methyl-5-[(phenylsulfonyl)methyl]phenoxy]methyl]phenyl]methyl]-2-pyrrolidinemethanol, is a novel Sphingonise Kinas 1 (SphK1, SK1) inhibitor.
Enzyme inhibitor
This potent SphK1 inhibitor (FWHCl-Salt = 502.07 g/mol; CAS 1706522-79- 3; Solubility: 10 mM in H2O, with gentle warming; 100 mM in DMSO), also named (2R)-1-[[(4-[[3-methyl-5-[(phenylsulfonyl)methyl]phenoxy] methyl]phenyl]methyl]-2-pyrrolidinemethanol hydrochloride, selectively targets sphingosine kinase 1 (IC50 = 2 nM; Ki = 3.6 nM). The latter phosphorylates sphingosine to form sphingosine-1-phosphate (S1P), a lipid messenger with both intracellular functions (regulating cell proliferation and survival) and extracellular functions (as a ligand for EDG1, or sphingosine-1-phosphate receptor 1). PF-543 also exhibits >100-fold selectivity for Sphk1 over Sphk2 as well as >5000 fold selectivity over S1P1-5 receptors and 48 protein and lipid kinases. P 543 attenuates proliferation and induces necrosis in human colorectal cancer cells in vitro. It also suppresses human colorectal cancer cell line HCT-116 as a tumor xenograft growth in mice
