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Updated: Apr 21, 2026

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
Published on: June 8, 2022
Drugging sphingosine kinases
Webster L Santos1, Kevin R Lynch
1Department of Chemistry, Virginia Tech , Blacksburg, Virginia 24061, United States.
Abstract:
The transfer of the gamma phosphate from ATP to sphingosine (Sph) to generate a small signaling molecule, sphingosine 1-phosphate (S1P), is catalyzed by sphingosine kinases (SphK), which exist as two isoforms, SphK1 and SphK2. SphK is a key regulator of S1P and the S1P:Sph/ceramide ratio. Increases in S1P levels have been linked to diseases including sickle cell disease, cancer, and fibrosis. Therefore, SphKs are potential targets for drug discovery. However, the current chemical biology toolkit needed to validate these enzymes as drug targets is inadequate. With this review, we survey in vivo active SphK inhibitors and highlight the need for developing more potent and selective inhibitors.
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