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Updated: Jun 2, 2026

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
Published on: June 8, 2022
Discovery, design and synthesis of the first reported potent and selective sphingosine-1-phosphate 4 (S1P4) receptor
Miguel Guerrero1, Mariangela Urbano, Subash Velaparthi
1Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, United States.
Abstract:
Selective S1P(4) receptor antagonists could be novel therapeutic agents for the treatment of influenza infection in addition to serving as a useful tool for understanding S1P(4) receptor biological functions. 5-(2,5-Dichlorophenyl)-N-(2,6-dimethylphenyl)furan-2-carboxamide was identified from screening the Molecular Libraries-Small Molecule Repository (MLSMR) collection and selected as a promising S1P(4) antagonist hit with moderate in vitro potency and high selectivity against the other family receptor subtypes (S1P(1-3,5)). Rational chemical modifications of the hit allowed the disclosure of the first reported highly selective S1P(4) antagonists with low nanomolar activity and adequate physicochemical properties suitable for further lead-optimization studies.
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