title: Structure-Activity Relationship Studies and Molecular Modeling of Naphthalene-Based Sphingosine Kinase 2 Inhibitors.
abstract: The two isoforms of sphingosine kinase (SphK1 and SphK2) are the only enzymes that phosphorylate sphingosine to sphingosine-1-phosphate (S1P), which is a pleiotropic lipid mediator involved in a broad range of cellular processes including migration, proliferation, and inflammation. SphKs are targets for various diseases such as cancer, fibrosis, and Alzheimer's and sickle cell disease. Herein, we disclose the structure-activity profile of naphthalene-containing SphK inhibitors and molecular modeling studies that reveal a key molecular switch that controls SphK selectivity.
authors.affiliation: Department of Chemistry, Department of Biochemistry, and Virginia Tech Center for Drug Discovery, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: Molly D
authors.initials: MD
authors.lastname: Congdon
authors.affiliation: Department of Pharmacology, University of Virginia , Charlottesville, Virginia 22908, United States.
authors.forename: Yugesh
authors.initials: Y
authors.lastname: Kharel
authors.affiliation: Department of Chemistry, Department of Biochemistry, and Virginia Tech Center for Drug Discovery, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Brown
authors.affiliation: Department of Chemistry, Department of Biochemistry, and Virginia Tech Center for Drug Discovery, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: Stephanie N
authors.initials: SN
authors.lastname: Lewis
authors.affiliation: Department of Chemistry, Department of Biochemistry, and Virginia Tech Center for Drug Discovery, Virginia Tech , Blacksburg, Virginia 24061, United States.
authors.forename: David R
authors.initials: DR
authors.lastname: Bevan
authors.affiliation: Department of Pharmacology, University of Virginia , Charlottesville, Virginia 22908, United States.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Lynch
authors.affiliation: Department of Chemistry, Department of Biochemistry, and Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg, Virginia 24061, United States; Department of Chemistry, Department of Biochemistry, and Virginia Tech Center for Drug Discovery, Virginia Tech, Blacksburg, Virginia 24061, United States.
authors.forename: Webster L
authors.initials: WL
authors.lastname: Santos
keywords: Sphingosine; molecular docking; sphingosine kinase; sphingosine-1-phosphate; structure−activity relationship