sphingosine

Erythro-sphingosine, (+)- is a cell-permeable and reversible inhibitor of protein kinase C (IC50: 12 µM) and enhances Src kinase activity.

C12-Sphingosine is a short-chain homologue of Sphingosine. It effectively inhibits the activity of serine palmitoyltransferase in primary cultured cerebellar cells.

Sphingosines are long-chain base precursors of cellular sphingolipids used directly in the synthesis of ceramide, which in combination with sialic acid forms ganglioside. Sphingosine can exist in four stereoisomers, however only sphingosine occurs naturally. Compared to other sphingolipids throughout the body, which are predominantly composed of C-18 sphingosine, only central nervous system (CNS) gangliosides contain significant amounts of sphingosine. The concentration of sphingosine within mammalian brain gangliosides apparently increases with developmental maturation. Furthermore, the ratio of C-18 to C-20 sphingosine in the brain is thought to be related to some nervous system degeneration processes.

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 (d18:1), an amino alcohol, is chiefly recognized for its 18-carbon unsaturated hydrocarbon chain. Nevertheless, in mammalian tissues, both sphingosine and its variant, dihydrosphingosine, feature hydrocarbon chains ranging from 12 to 26 carbons. Sphingosine (d15:1) represents a naturally rare variant, serving as an internal standard for chromatographic or spectrometric analyses of sphingoid compounds.

Sphingosine (d16:1), an unconventional sphingolipid, is synthesized through enzymatic reactions starting with the condensation of myristoyl-CoA and serine by serine palmitoyltransferase long-chain base subunit 3 (SPTLC3), which shows a preference for myristoyl-CoA. This compound is found in minute quantities in its free form in human plasma and as a component of various plasma sphingolipids, such as sphingosine-1-phosphate, ceramides, sphingomyelins, and in brain cerebrosides, albeit at lower concentrations than the more common d18:1 sphingoid base. Sphingosine (d16:1) acts as an inhibitor of PKC in mixed micelle assays and diminishes superoxide production triggered by phorbol 12-myristate 13-acetate in isolated human neutrophils, as well as inhibiting the growth of CHO cells with IC50 values of 1 and 3.2 µM, respectively. Additionally, the concentration of sphingolipids containing sphingosine (d16:1) in the plasma is linked to the dietary consumption of saturated fatty acids and protein among ethnic Chinese populations.

Sphingosine (d14:1) is a bioactive sphingolipid that has been found in B. mori (silkworm), P. clarkii (crayfish), and A. aurita (jellyfish) extracts. It increases the germination rate of N. rileyi, an entomopathogenic fungus, with an EC50 value of 10.2 nM. Sphingosine (d14:1) inhibits protein kinase C (PKC) in vitro (IC50 = 7.3 mol%) as well as superoxide generation induced by phorbol 12-myristate 13-acetate in neutrophils and reduces growth of CHO cells (IC50s = 19 and 8 μM, respectively).

D-erythro-Sphingosine (trans-4-Sphingenine) is a protein kinase C (PKC) inhibitor. D-erythro-Sphingosine (Erythrosphingosine) is also a PP2A activator

L-threo-Sphingosine C-18 is a protein kinase C inhibitor.

D-erythro-Sphingosine hydrochloride, also known as Erythrosphingosine, serves as a specific TRPM3 activator and induces retinoblastoma protein dephosphorylation.

Sphingosine (d17:1) (C17 Sphingosine) is a 17-carbon sphingolipid found in human skin that can be phosphorylated by sphingomyelin kinase.Sphingosine C-17 can be used as an internal standard to perform spectroscopic analysis of sphingolipids.

Sphingosine-1-phosphate (S1P) is an agonist for S1P1-5 receptors and a ligand for GPR3, GPR6, GPR12.Sphingosine-1-phosphate is an intracellular second messenger that mobilises Ca2+ as an extracellular ligand for G-protein coupled receptors. Sphingosine-1-phosphate is an important lipid mediator generated from sphingosine (HY-113498) or other membrane phospholipids.

Sphingosine phosphorylcholine is a wound healing agent.

PF-543 (Sphingosine Kinase 1 Inhibitor II), a novel sphingosine-competitive inhibitor of SphK1, inhibits SphK1 with IC50 and Ki of 2.0 nM and 3.6 nM.

C12-Ceramide (C12 Ceramide (d18:1/12:0)), a ceramide present in the protective membranes surrounding umbilical cord blood vessels in infants born to women with pre-eclampsia, can be used to assess the level of ASM activity in the plasma of patients with Niemann-Pick disease.

S1PL-IN-31 is a dual-function chemical compound acting as an inhibitor of sphingosine-1-phosphate (S1P) lyase with an IC50 value of 210 nM and as an antagonist of the Smoothened (Smo) receptor with an IC50 of 440 nM. Demonstrating therapeutic potential, this compound, at a dosage of 2 mg/kg per day, effectively mitigates cervical and thoracic lymphocyte infiltration and neuromuscular weakness in rats suffering from experimental autoimmune encephalomyelitis (EAE), a condition triggered by the MOG29-152 peptide from myelin oligodendrocyte glycoprotein. Additionally, it significantly decreases the total lymphocyte count, including reductions in subsets of CD4+ T cells, CD8+ T cells, and B cells. At a higher dosage of 100 mg/kg, S1PL-IN-31 elevates S1P levels within the heart and lymph nodes, while doses of 3 and 10 mg/kg per day notably lower heart rates in female rats, showcasing its multifaceted biological impacts and potential for clinical application.

Psychosine (Galactosylsphingosine) is a PKC inhibitor, a substrate for the enzyme galactosylceramide cerebrosidase (GALC), and a potential biomarker of Krabbe's disease.Psychosine is highly cytotoxic and induces cell death in a variety of cells.

C20 Ceramide (N-Arachidoyl-D-sphingosine) is a 20:0 ceramide found in the brain that crosses the blood-brain barrier to activate microglia and induce depressive-like behavior.

C18 Ceramide-1-phosphate (d18:1/18:0) is a long-chain molecule identified in murine skin known to promote the migration of mouse bone marrow-derived multipotent stromal cells and human umbilical vein endothelial cells (HUVECs) at concentrations of 0.5 to 5 µM. It exhibits elevated levels in CFPAC-1 pancreatic ductal adenocarcinoma cells compared to pancreatic cancer stem cells, and its myocardial concentration is heightened in Langendorff isolated perfused mouse hearts under an ex vivo ischemia model.

C8 Ceramide, a cell-permeable analog, is analog to naturally occur ceramides.

C14 Ceramide (d18:1/14:0) is an endogenous ceramide produced by ceramide synthetase 6, which can be used for Parkinson's research.

PF-543 Citrate is an inhibitor of sphingosine-competitive SPHK1(IC50 of 2 nM ).

SOCLAC, a derivative of the acid ceramidase inhibitor SABRAC, functions as an irreversible inhibitor of acid ceramidase with an inhibition constant (Ki) of 40.2 nM.

Phorbol 12-myristate 13-acetate (PMA) belongs to the phorbol ester group of natural products and is an activator of PKC, SphK, and NF-κB. Phorbol 12-myristate 13-acetate induces THP1 cell differentiation.

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

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.

D-Glucosyl-β-1,1′-N-palmitoylsphingosine (C16 Glucosyl(β) Ceramide (d18:1/16:0)) serves as an endogenous ligand for the Macrophage-Inducible C-type Lectin (Mincle), exhibiting immunostimulatory properties [1].

3'-sulfo Galactosylsphingosine is a form of sulfatide that is lacking the fatty acyl group. It decreases migration and adhesion of B35 neuroblastoma cells and increases cell rounding when used at a concentration of 20 μM. It also inhibits PKC and cytochrome c oxidase activity when used at concentrations of 150 and 50-100 μM, respectively. 3'-sulfo Galactosylsphingosine accumulates in patients with metachromatic leukodystrophy, a lysosomal storage disorder characterized by arylsulfatase A (ASA) deficiency leading to progressive demyelination and neuromotor deficits. In mice lacking ASA, levels of 3'-sulfo galactosylsphingosine increase after one month of age followed by demyelination and neuromotor deficits. 3'-sulfo Galactosylsphingosine has been used as a standard for the quantification of 3'-sulfo galactosylsphingosine by LC-MS.

1-Deoxysphingosine (m18:1(4E)) is an atypical sphingolipid that contains a double bond at the 4E native position and is formed when serine palmitoyltransferase condenses palmitoyl-CoA with alanine instead of serine during sphingolipid synthesis.1,2 Plasma levels of 1-deoxysphingosine (m18:1(4E)) are increased in patients with chronic idiopathic axonal neuropathy (CIAP) and diabetic distal symmetrical polyneuropathy (DSPN).3 |1. Steiner, R., Saied, E.M., Othman, A., et al. Elucidating the chemical structure of native 1-deoxysphingosine. J. Lipid Res. 57(7), 1194-1203 (2016).|2. Alecu, I., Othman, A., Penno, A., et al. Cytotoxic 1-deoxysphingolipids are metabolized by a cytochrome P450-dependent pathway. J. Lipid Res. 58(1), 60-71 (2017).|3. Hube, L., Dohrn, M.F., Karsai, G., et al. Metabolic syndrome, neurotoxic 1-deoxysphingolipids and nervous tissue inflammation in chronic idiopathic axonal polyneuropathy (CIAP). PLoS One 12(1):e0170583, (2017).

C24 Phytosphingosine (t18:0/24:0) is a phytoceramide, which is a family of sphingolipids found in the intestine, kidney, and extracellular spaces of the stratum corneum of the mammalian epidermis. C24 Phytosphingosine (t18:0/24:0) is composed of a phytosphingosine backbone amine-linked to a C24 fatty acid chain. It has been used with other ceramides to create stratum corneum substitutes to study percutaneous penetration and psoriasis in vitro. In a stratum corneum model of healthy skin, the incorporation of long-chain-containing phytoceramides, such as C24 phytosphingosine (t18:0/24:0), increases permeability of the membrane in comparison with incorporation of dihydroceramides.

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 can be used in experimental autoimmune encephalomyelitis, arterial Ex26 is used in experimental autoimmune encephalomyelitis, atherosclerosis and gastric cancer.

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.

CYM50374 inhibits Sphingosine-1-phosphate receptor 4 (S1P4 ) with an IC50 of µM.

Ceranib1 is an inhibitor of ceramidase. It inhibits the proliferation of ovarian cancer cells. Ceranib1 inhibits ceramidase activity toward an exogenous ceramide analog, induces the accumulation of multiple ceramide species, decreases levels of S1P and sphingosine.

TASP 0277308 is a potent and selective sphingosine 1-phosphate 1 (S1P1) receptor antagonist (IC50 = 7.8 nM). TASP 0277308 inhibits S1P-induced chemotaxis (IC50 = 1.1-1.6 nM), HUVEC cell proliferation (IC50 = 3-3.6 nM) and suppresses angiogenesisin vivo. TASP 0277308 also blocks VEGF-induced tube-formation of HUVECsin vitroand reverses or impairs the development of arthritis or mechano-allodynia.

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

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.