Abstract
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.
Keywords:
Cancer; Dansyl; Inhibitor; Label; PF-543; Sphingosine kinase.
Copyright © 2018 Elsevier B.V. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Binding Sites
-
Fluorescent Dyes / chemistry*
-
Methanol
-
Molecular Docking Simulation
-
Molecular Structure
-
Phosphatidylcholines / chemistry*
-
Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors*
-
Protein Binding
-
Protein Kinase Inhibitors / chemistry*
-
Pyrrolidines / chemistry*
-
Spectrometry, Fluorescence
-
Structure-Activity Relationship
-
Sulfones / chemistry*
-
Xylenes / chemistry
Substances
-
1-myristoyl-2-(12-((5-dimethylamino-1-naphthalenesulfonyl)amino)dodecanoyl)-sn-glycero-3-phosphocholine
-
Fluorescent Dyes
-
PF-543
-
Phosphatidylcholines
-
Protein Kinase Inhibitors
-
Pyrrolidines
-
Sulfones
-
Xylenes
-
Phosphotransferases (Alcohol Group Acceptor)
-
sphingosine kinase
-
3,5-xylenol
-
Methanol