s1p5

ASP-4058 is a selective, safe, and orally active second-generation agonist of sphingosine phosphate receptors 1 and 5 (S1P1 and S1P5).ASP-4058 ameliorates experimental autoimmune encephalomyelitis in mice.

AMG-369 (AMG 247) is an S1P1/S1P5 dual agonist that delays the onset of experimental autoimmune encephalomyelitis in rats. encephalomyelitis in rats.

CYM50308 is a high affinity agonist of sphingosine-1-phosphate receptor 4 (S1P4-R) (EC50: 56 nM). CYM50308 has no activity at S1P1-R, S1P2-R and S1P3-R subtypes at concentrations up to 25 μM and it shows 37-fold more selective for S1P4-R than S1P5-R.

BAF312 (Siponimod (BAF-312)), a next-generation S1P receptor modulator, is specific for S1P1 and S1P5 receptors with EC50 of 0.39 nM and 0.98 nM, respectively. The specificity of BAF312 for S1P1 and S1P5 receptors exhibits >1000-fold over S1P2, S1P3 and S1P4 receptors.

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.

S1P5 receptor antagonist 1 is a selective antagonist of the S1P5 receptor that is capable of crossing the blood-brain barrier. It has an EC50 of 0.1 nM and a Ki of 4.4 nM. This compound inhibits the migration of natural killer cells towards sphingosine 1-phosphate in vitro, while having no effect on T cell migration. S1P5 receptor antagonist 1 is applicable in central nervous system disease research.

S1P5 Receptor Agonist-1 (example 6) is a highly potent and selective agonist for the S1P5 receptor, exhibiting an EC50 value of 20 nM.

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).

S1PR5-IN-1 (Compound 7a) is a selective S1PR5 inhibitor capable of crossing the blood-brain barrier, with an IC₅₀ of 85.4 nM. It exhibits exceptional binding affinity to S1PR5, with Kd values of 2.2 nM for recombinant human S1PR5 cell membranes, 4.6 nM for C57BL/6 mouse brains, and 27.6 nM for human cerebral cortex. S1PR5-IN-1 is applicable in researching neurodegenerative diseases such as multiple sclerosis.

CYM-5478 is a highly selective S1P2 agonist with an EC50 value of 119 nM in the TGF-α detachment test and can reduce the toxicity of cisplatin to neurogenic cell lines.

Ponesimod (ACT-128800) is an orally available sphingosine-1-phosphate receptor 1 (S1PR1, S1P1) agonist with potential immunomodulating activity.

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).

RP101442, the active metabolite of Ozanimod, is a selective and potent agonist of the sphingosine-1-phosphate receptor 1 (S1PR1), displaying EC50 values of 2.6 nM for S1PR1 and 171 nM for S1PR5.

CYM50260 is a potent and highly selective agonist of the sphingosine-1-phosphate 4 receptor (S1P4-R, EC50= nM), exhibiting no activity against S1P1-R, S1P2-R, S1P3-R, and S1P5-R.

RP-001 is a selective agonist of picomolar short-acting S1P1 (EDG1)(EC50 of 9 pM), has little activity on S1P2-S1P4 and only moderate affinity for S1P5.

RP-001 hydrochloride is a selective agonist of picomolar short-acting S1P1 (EDG1)(EC50 of 9 pM), has little activity on S1P2-S1P4 and only moderate affinity for S1P5.

FTY720 (S)-Phosphate is the active stereoisomeric phosphate derivative of FTY720 that acts as a potent modulator of sphingosine-1-phosphate (S1P) receptors. FTY720 (S)-Phosphate binds to S1P receptor subtypes S1P1, S1P3, S1P4, and S1P5 with Ki values of 2.1, 5.9, 23, and 2.2 nM respectively, causing receptor internalization on lymphocytes， preventing S1P-mediated lymphocyte egress from lymphoid tissues. FTY720 (S)-Phosphate also enhances endothelial barrier integrity, stimulates transporters such as Abcb1 and Abcc1, and inhibits cytosolic phospholipase A2 activity, highlighting its multifunctional pharmacological properties, making it an compound of interest in the research of diseases including multiple sclerosis, autoimmune diseases and cancer.

VPC 23019 is a competitive antagonist at the S1P1 and S1P3 receptors (pKi= 7.86 and 5.93, respectively). It is also an agonist at the S1P4 and S1P5 receptors (pEC50= 6.58 and 7.07, respectively).

Etrasimod arginine (APD334 arginine) is an orally active S1P receptor modulator, acting as a full agonist of the S1P1 receptor with partial agonist activity at S1P4 and S1P5, and can be used in research on autoimmune and inflammatory diseases such as ulcerative colitis.

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)

Azido-FTY720 (azido-Fingolimod) is an analogue of FTY720 featuring an azido group suitable for click chemistry reactions. FTY720 is an orally available S1P analogue and S1P1R modulator capable of crossing the blood-brain barrier (BBB), reducing neuroinflammation, and is indicated for multiple sclerosis (MS).

A-971432 is a sphingosine-1-phosphate receptor 5 (S1P5) agonist that is selective for S1P5 over S1P1 and S1P3 (IC₅₀s = 0.006, 0.362, and >10 µM, respectively). It inhibits forskolin-induced cAMP production in CHO cells expressing S1P5 (EC50 = 4.1 nM). A-971432 (1 µM) increases electrical resistance of hCMEC/D3 cells in an in vitro blood-brain barrier model, indicating enhanced barrier integrity, and attenuates blood-brain barrier leakage in an R6/2 transgenic mouse model of Huntington's disease when administered at a dose of 0.1 mg/kg.[1] [2] A-971432 (0.1 mg/kg per day, i.p.) decreases the number of errors made in a horizontal ladder task and increases latency to fall in the rotarod test in R6/2 mice. It also increases spontaneous alternation in the t-maze in aged mice when administered at a dose of 0.1 mg/kg.[1] References [1].Hobson, A.D., Harris, C.M., van der Kam, E.L., et al. Discovery of A-971432, an orally bioavailable selective sphingosine-1-phosphate receptor 5 (S1P5) agonist for the potential treatment of neurodegenerative disorders. J. Med. Chem. 58(23), 9154-9170 (2015).[2]. Di Pardo, A., Castaldo, S., Amico, E., et al. Stimulation of S1PR5 with A-971432, a selective agonist, preserves blood-brain barrier integrity and exerts therapeutic effect in an animal model of Huntington's disease. Hum. Mol. Genet. 27(14), 2490-2501 (2018).