Lysophospholipid (S1P) receptors in GtoPdb v.2023.1

Sphingosine 1-phosphate (S1P) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Lysophospholipid [96]) are activated endogenous lipid sphingosine (S1P). Originally cloned orphan members of endothelial differentiation gene (edg) family [16, 123], currently designated S1P1R through S1P5R [73, 16, 123]. Their nomenclature has been codified human S1PR1, S1PR2, etc. (HUGO Gene Nomenclature Committee, HGNC) and S1pr1, S1pr2, for mice (Mouse Genome Informatics Database, MGI) to reflect species receptor function. All S1P (S1PRs) have knocked-out in constitutively some cases, conditionally. S1PRs, particularly S1P1, expressed throughout all mammalian organ systems. Ligand delivery occurs via two known carriers (or "chaperones"): albumin HDL-bound apolipoprotein M (ApoM), latter which elicits biased agonist signaling S1P1 multiple cell types [18, 53]. The five chaperones, active cellular metabolism complicated analyses ligand binding native Signaling pathways physiological roles characterized radioligand heterologous expression systems, targeted deletion different most recently, mouse models that report vivo activation [101, 103]. structures [180, 69, 108, 184], S1P2 [32], S1P3[116, 187], S1P5 [110, 185] solved, confirmed aspects binding, specificity, activation, determined previously biochemical genetic studies [69, 17]. fingolimod (FTY720), first FDA-approved drug target any lysophospholipid receptors, binds a phosphorylated metabolite four was oral therapy sclerosis (MS) [35]. Second-generation S1PR modulators siponimod, ozanimod, ponesimod also FDA approved treatment various MS forms In 2021, ozanimod became modulator be ulcerative colitis [145]. mechanisms action other S1PR-modulating drugs now development include S1PRs e.g., immune nervous although precise nature their interactions requires clarification [141, 37, 63, 64].