The sphingosine 1-phosphate (S1P) receptor S1P3 has roles in vasodilation, epithelial barrier function, cardioprotection, fibrosis, immunity, and inflammation. CYM 5541 is a selective, allosteric agonist of S1P3 (EC50 = 72-132 nM). It less effectively activates S1P1 (EC50 = 28-38 μM) and is ineffective at S1P2, S1P4, and S1P5 as well as a panel of other receptors, ion channels and transporters.
CYM 5541, is a selective allosteric agonist of SAR and S1P3 receptors.
CYM-5541 is an allosteric agonist selective for the Sphingosine 1-phosphate (S1P) S1P3 receptor subtype. CYM-5541 occupies a different chemical space in the ligand binding pocket of S1P3 than S1P does, a lower hydrophobic region around transmembrane helix TM6. CYM-5541 shows great selectivity and stability with an EC50 of between 72 and 132 nM compared to S1P1 EC50 > 10 μM, S1P2 EC50 > 50 μM, S1P4 EC50 > 50 μM, and S1P5 EC50 > 25 μM and no significant activities for a panel of 55 GPCRs, ion channels, and transporters.
[1] Probe Development Efforts for an Allosteric Agonist of Sphingosine 1-phosphate Receptor 3 (S1P3); Probe Reports from the NIH Molecular Libraries Program
[2] EUIJUNG JO. Novel Selective Allosteric and Bitopic Ligands for the S1P3 Receptor[J]. ACS Chemical Biology, 2012, 7 12: 1975-1983. DOI:
10.1021/cb300392z
