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Updated: Sep 23, 2025

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
Published on: June 8, 2022
Synthesis and Evaluation of Serinolamide Derivatives as Sphingosine-1-Phosphate-1 (S1P1) Receptor Agonists
Sun Jun Park1,2, Jushin Kim1,3, Jaehwan Kim1,2
1Convergence Research Center for Brain Science, Korea Institute of Science & Technology (KIST), Seoul 02792, Korea.
Abstract:
Sphingosine-1-phosphate-1 (S1P1) receptor agonists are well-known drugs for treating multiple sclerosis (MS) caused by autoreactive lymphocytes that attack the myelin sheath. Therefore, an effective therapeutic strategy is to reduce the lymphocytes in the blood by inducing S1P1 receptor internalization. We synthesized serinolamide A, a natural product of the sea, and performed S1P1 receptor internalization assay to evaluate functionally antagonistic S1P1 receptor agonist activity. In order to synthesize derivatives with better efficacy than serinolamide A and B, new derivatives were synthesized by introducing the phenyl ring moiety of fingolimod. Among them, compounds 19 and 21 had superior S1P1 agonistic effects to serinolamide. We also confirmed that compound 19 effectively inhibited lymphocyte outflow in peripheral lymphocyte count (PLC) assay.
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