Table 1.
Characteristics and physiological functions of G protein-coupled S1P receptor subtypes (SPR1-5) and modulator drugs under evaluation [3, 6, 22]
| S1PR1 | S1PR2 | S1PR3 | S1PR4 | S1PR5 | |
|---|---|---|---|---|---|
| Expression | B, T, and dendritic cells, heart tissue, neurons, endothelium | Endothelium, heart tissue, smooth muscle vessels, tumoral cells, lung fibroblasts | Smooth muscle vessels, endothelium, heart tissue, lung fibroblasts | T cells, dendritic cells; breast tumoral cells | Natural killer, endothelial cells, oligodendrocytes |
| Signaling | Akt, ERK, Rac | Akt, NFkB Rho/ROCK | NFkB | ERK | Akt, Rho/ROCK |
| Clinical relevance | Immune modulation, bradycardia, tumor maintenance, theoretical breast cancer prognosis | Kidney injury, tumor maintenance, fibroblast contraction | Hypertension, tumor maintenance | Immune modulation | Immune modulation, myelination |
| Vascular system | Endothelial barrier integrity, heart rate control, angiogenesis | Regulates vascular tone and endothelial barrier | Modulates endothelial barrier, vasoconstriction, heart rate control. Might induces vasorelaxation | Vasoconstriction | |
| Immune system | Lymphocyte and dendritic cell migration. Might induce suppression of T Reg cells, promoting Th1 development and Th17 polarization | B cell migration in the follicle promoting the local confinement of germinal center B cells | Location of immature B cells and progenitors within the bone marrow |
Regulation of DC function and Th17 differentiation Neutrophil trafficking Inhibition of effector cytokines, secretion of IL-10 |
Natural killer trafficking |
| Nervous system | Neural and oligodendrocyte function | Neural migration and cell function | Blood brain integrity, oligodendrocyte function | ||
| Other outcomes | Nociception, proliferation | Fibrosis, inhibition of B-cell survival, proliferation | Fibrosis, proliferation | ||
| S1PR agonists | AMG 369, amiselimod, ASP0028, ASP4058, AUY954, cenerimod. ceralifimod, CS-077, CS-2100, CYM544, etrasimod, fingolimod, GSK1842799, GSK2018682, mocravimod, ozanimod, Ponesimod, RP-001, SEW2871, siponimod, ST-968, ST-1071, Syl948, TC-G 1006, TC-SP14, amgen 8,14 | Fingolimod, ST-968, ST-1071 | Amiselimod, etrasimod, fingolimod | A-971432, AMG 369, amiselimod, ASP0028, ASP4058, cerafimod, etrasimod, fingolimod, GSK2018682, ozanimod, siponimod | |
| S1PRs antagonists | AD2900, Ex26, NIBR-0213, TASP0277308, VPC23019, W146 | AB1, AD2900, JTE-013 | 7H9, AD2900, CAY10444, SPM-354, TY-52156, VPC23019 | AD2900 | AD2900 |
ERK extracellular signal-regulated kinases, Akt protein kinase B, Rac subfamily of the Rho family of GTPases, Rho/ROCK Rho-associated kinase is an effector of the small GTPase, NFkB nuclear factor kappa light-chain enhancer of activated B cells, Treg regulatory T cell, Th T helper cell, STAT-3 signal transducer and activator of transcription 3, IL-10 interleukin 10