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Updated: Feb 4, 2026

A Pipeline to Investigate the Structures and Signaling Pathways of Sphingosine 1-Phosphate Receptors
Published on: June 8, 2022
Identification and Structure-Activity Relationship (SAR) of potent and selective oxadiazole-based agonists of
Tianqi Liu1, Jing Jin1, Yonghui Chen1
1State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China.
Abstract:
Agonism of S1P1 receptor has been proven to be responsible for peripheral blood lymphopenia and elicts the identification of various S1P1 modulators. In this paper we described a series of oxadiazole-based S1P1 direct-acting agonists disubstituted on terminal benzene ring, with high potency for S1P1 receptor and favorable selectivity against S1P3 receptor. In addition, two representative agents named 16-3b and 16-3g demonstrated impressive efficacy in lymphocyte reduction along with reduced effect on heart rate when orally administered. Furthermore, these compounds have been shown to possess desired pharmacokinetic (PK) and physicochemical profiles. The binding mode between 16-3b and the activated S1P1 model was also studied.
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