sphingosine 1-phosphate (s1p)

Ozanimod (RPC-1063) (RPC1063) is a specific oral S1P Receptor 1 modulator. Ozanimod has been used in trials studying the treatment of Crohn's Disease, Ulcerative Colitis, Multiple Sclerosis, and Relapsing Multiple Sclerosis.

Sphingosine-1-phosphate (S1P) is an agonist for S1P1-5 receptors and a ligand for GPR3, GPR6, and GPR12. As an intracellular second messenger, it mobilizes Ca2+ and acts as an extracellular ligand for G-protein coupled receptors. This important lipid mediator is generated from sphingosine or other membrane phospholipids.

LX-2931(LX-3305) is a sphingosine-1-phosphate cleavage enzyme (S1P) inhibitor for the treatment of rheumatoid arthritis.

TASP 0277308 is a selective and potent inhibitor of sphingosine 1-phosphate receptor 1 ( S1P1) with immunomodulatory and anticancer activity that inhibits S1P- as well as VEGF-induced cellular responses and blocks VEGF-induced tube formation. TASP 0277308 is used in the study of immune and cardiovascular disorders.

SLP9101555 is a potent and selective sphingosine kinase 2 (SphK2) inhibitor with a Ki of 90 nM.SLP9101555 has a high affinity for SphK2, which is 200-fold higher than that of SphK1.SLP9101555 dramatically reduces extracellular S1P sphingosine 1-phosphate (S1P) levels.

Fingolimod hydrochloride (FTY720) , a novel immune modulator, is a sphingosine 1-phosphate (S1P) antagonist (IC50: 0.033 nM in K562 and NK cells).

Fingolimod (FTY-720A) is an antagonist of sphingosine 1-phosphate (S1P) (IC50 of 0.033 nM in K562 and NK cells).

4-Deoxypyridoxine (4-DPD) is a vitamin B6 antimetabolite with diverse biological activities. It inhibits transport of pyridoxine , pyridoxal, and pyridoxamine in and reduces growth of S. carlsbergensis cells. 4-DPD inhibits sphingosine-1-phosphate (S1P) lyase and reduces cyclic stretch-induced apoptosis in alveolar epithelial MLE-12 cells. 4-DPD (5 mg, i.p.) reduces lysyl oxidase activity by 26% and reduces collagen and elastin crosslinking, resulting in limb abnormalities in chick embryos. It decreases latency to first seizure in mice (ED50 = 1 mmol kg) and increases the occurrence and duration of myoclonic responses in baboons with photosensitive epilepsy. 4-DPD reduces TNF-α and IL-6 production in mice infected with T. spiralis.

ASP1126 is a selective and orally active sphingosine-1-phosphate (S1P) agonist with EC50 values of 7.12 nM and 517 nM for hS1P1 and hS1P3, respectively.

PF-543 Citrate (Sphingosine Kinase 1 Inhibitor II Citrate) is a selective and potent inhibitor of sphingosine kinase 1 (SPHK1) and is an efficient inhibitor of 1-phosphate sphingosine (S1P) formation. It possesses anticancer, antifibrotic, and anti-inflammatory activities and can be used in research on colorectal cancer.

Cenerimod (ACT-334441) is an orally active, selective, and potent sphingosine 1-phosphate receptor (S1P1) agonist (EC50: 1 nM).Cenerimod inhibits multiple S1P isoforms and can be used to study murine experimental autoimmune encephalomyelitis (EAE) and murine scleroderma.

Ceralifimod (ONO-4641) is a potent agonist for sphingosine 1-phosphate receptors 1 and 5 (EC50s: 27.3, 334 pM for human S1P receptor 1 and 5).

TRV045 is a selective agonist of the sphingosine-1-phosphate (S1P) subtype 1 receptor and does not impact lymphocyte trafficking. It possesses antiepileptic properties.

ML-178, a dichlorobenzene, is a potent and selective agonist of sphingosine-1-phosphate receptor 4 (S1PR4), with an EC50 of 46 nM, and has no effect on other S1P receptors at a concentration of 25 μM.

Ex26 (S1P1-IN-Ex26) is a selective and potent sphingosine 1-phosphate receptor 1 (S1P1) antagonist that disrupts SR-B1-S1PR1 interactions and inhibits S1P-S1PR1 signaling. Ex26 is used in experimental autoimmune encephalomyelitis, atherosclerosis, and gastric cancer.

SPM-242 is an orthosteric agonist of Sphingosine 1-phosphate (S1P) and a bitopic antagonist. S1P is a lysophospholipid signaling molecule that regulates important biological functions, including vascular development and lymphocyte trafficking, by activat

A6770 is an inhibitor of sphingosine-1-phosphate (S1P) lyase.1It induces accumulation of [3H]sphinganine-1-phosphate ([3H]dhS1P), an S1P lyase substrate, in IT-79MTNC3 cells that endogenously express high levels of S1P lyase (EC50= <0.01 μM), an effect that is reduced in the presence of vitamin B6(EC50= <100 μM). 1.Ohtoyo, M., Tamura, M., Machinaga, N., et al.Scintillation proximity assay to detect the changes in cellular dihydrosphingosine 1-phosphate levelsLipids51(10)1207-1216(2016)

Lysosphingomyelin is an endogenous bioactive sphingolipid and a constituent of lipoproteins.1,2It is produced by the removal of the acyl group from sphingomyelin by a deacylase and acts as a precursor in the biosynthesis of sphingosine-1-phosphate . D-erythroLysosphingomyelin is an agonist of the S1P receptors S1P1, S1P2, and S1P3(EC50s = 167.7, 368.1, and 482.6 nM, respectively, for the human receptors).3It is also an agonist of the orphan receptor ovarian cancer G protein-coupled receptor 1 (ORG1) that induces calcium accumulation in cells overexpressing OGR1 (EC50= ~35 nM).4Levels of D-erythrolysosphingomyelin are increased in skin isolated from patients with atopic dermatitis, as well as postmortem brain from patients with Niemann-Pick disease type A, but not type B.2,5L-threolysosphingomyelin is also an S1P1-3agonist (EC50s = 19.3, 131.8, and 313.3 nM, respectively).3This product is a mixture of D-erythroand L-threolysosphingomyelin. [Matreya, LLC. Catalog No. 1321] 1.Ito, M., Kurita, T., and Kita, K.A novel enzyme that cleaves the N-acyl linkage of ceramides in various glycosphingolipids as well as sphingomyelin to produce their lyso formsJ. Biol. Chem.270(41)24370-24374(1995) 2.Nixon, G.F., Mathieson, F.A., and Hunter, I.The multi-functional role of sphingosylphosphorylcholineProg. Lipid Res.47(1)62-75(2008) 3.Im, D.-S., Clemens, J., Macdonald, T.L., et al.Characterization of the human and mouse sphingosine 1-phosphate receptor, S1P5 (Edg-8): Structure-activity relationship of sphingosine1-phosphate receptorsBiochemistry40(46)14053-14060(2001) 4.Meyer zu Heringdorf, D., Himmel, H.M., and Jakobs, K.H.Sphingosylphosphorylcholine-biological functions and mechanisms of actionBiochim. Biophys. Acta1582(1-3)178-189(2002) 5.Rodriguez-Lafrasse, C., and Vanier, M.T.Sphingosylphosphorylcholine in Niemann-Pick disease brain: Accumulation in type A but not in type BNeurochem. Res.24(2)199-205(1999)

FTY720 is a derivative of ISP-1 (myriocin), a fungal metabolite of the Chinese herb Iscaria sinclarii as well as a structural analog of sphingosine. It is a novel immune modulator that prolongs allograft transplant survival in numerous models by inhibiting lymphocyte emigration from lymphoid organs. FTY720 is phosphorylated by sphingosine kinase, which then acts as a potent agonist at four of the sphingosine-1-phosphate (S1P) receptors (S1P1, S1P3, S1P4, and S1P5). Down-regulation of S1P1 receptors on T and B lymphocytes by FTY720 results in defective egress of these cells from spleen, lymph nodes, and Peyer's patch. azido-FTY720 is a highly photoreactive analog of FTY720 that can be used to identify receptor binding sites for this ligand.

C16 Sphingosine-1-phosphate (C16 S1P) is a derivative of sphingosine-1-phosphate that binds to S1P1/EDG-1, S1P3/EDG-3, and S1P2/EDG-5 receptors with affinities of 115%, 83%, and 103%, respectively, relative to S1P in CHO cells. C16 S1P was increased in postmortem primary open angle glaucoma trabecular meshwork samples.

Sphingosine-1-phosphate (S1P) is a bioactive lipid that exhibits a broad spectrum of biological activities including cell proliferation, survival, migration, cytoskeletal organization, and morphogenesis. It exerts its activity by binding to five distinct G protein-coupled receptors, S1P1 EDG-1, S1P2 EDG-5, S1P3 EDG-3, S1P4 EDG-6, and S1P5 EDG-8. W140 is an inactive enantiomer of W146, a selective S1P1 antagonist (Ki = 77 nM), that binds to the S1P1 receptor with a Ki of 4.6 μM (2a = W146; 2b = W140 in supplemental material). It exhibits no biological activity in vivo and can therefore serve as an effective control compound for experiments involving W146.

SAR247799 (S1P1 agonist 3) is a selective and G-protein-biased S1P1 agonist that activates downstream G-protein signaling pathways more preferentially than β-blocker proteins and internalized signaling pathways, activates S1P 1 on endothelial cells without causing receptor desensitization, and protects the endothelium without affecting lymphocyte populations, and can be used to study type 2 diabetes, endothelial dysfunction and vascular hyperpermeability.

Ozanimod hydrochloride (RPC-1063 hydrochloride) is an orally available, selective and potent sphingosine 1-phosphate (S1P) receptor modulator that shows high affinity for S1P1 and S1P5.Ozanimod has potential anticancer activity and can be used in the study of multiple sclerosis (MS), ulcerative multiple sclerosis (UMS), and other diseases. (MS), ulcerative colitis, coronavirus infections and myelodysplasia.

Siponimod (BAF-312) hemifumarate, a selective and potent modulator of sphingosine-1-phosphate (S1P) receptors, can be used in the study of multiple sclerosis (MS).