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Updated: May 15, 2026

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
Published on: June 8, 2022
Exploring amino acids derivatives as potent, selective, and direct agonists of sphingosine-1-phosphate receptor
Ghotas Evindar1, Hongfeng Deng, Sylvie G Bernier
1Department of Medicinal Chemistry, Praecis Pharmaceuticals Incorporated (Currently GlaxoSmithKline), 830 Winter Street, Waltham, MA 02451, USA. ghotas.x.evindar@gsk.com
Abstract:
In the quest to discover a potent and selective class of direct agonists to the sphingosine-1-phosphate receptor, we explored the carboxylate functional group as a replacement to previously reported lead phosphates. This has led to the discovery of potent and selective direct agonists with moderate to substantial in vivo lymphopenia. The previously reported selectivity enhancing moiety (SEM) and selectivity enhancing orientation (SEO) in the phenylamide and phenylimidazole scaffolds were crucial to obtaining selectivity for S1P receptor subtype 1 over 3.
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