pf-543 and 3-5-xylenol

PF-543 is a non-sphingosine analogue with inhibitory effect against SK1, based on a Ki of 4.3 nM and 130-fold selectivity for SK1 over SK2. Since the development of PF-543, animal studies demonstrated its valuable role in multiple sclerosis, myocardial infarction, and colorectal cancer. We synthesized labeled PF-543 for biochemical studies involving SK1. Overall, the 8-step synthetic route used 3,5-dimethylphenol as the starting material. A docking study of SK1 and SK1 inhibitory activity confirmed the structural similarity between the synthetic dansyl-PF-543 and PF-543. We also provide fluorescence spectra of dansyl-PF-543.

Topics: Binding Sites; Fluorescent Dyes; Methanol; Molecular Docking Simulation; Molecular Structure; Phosphatidylcholines; Phosphotransferases (Alcohol Group Acceptor); Protein Binding; Protein Kinase Inhibitors; Pyrrolidines; Spectrometry, Fluorescence; Structure-Activity Relationship; Sulfones; Xylenes