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Sphingosine-1-phosphate (S1P) receptor modulators act on S1PR1 to S1PR5, five G protein-coupled lipid receptors. In 1998 S1P was identified as a ligand of the orphan receptor endothelial differentiation gene 1 (EDG-1), now called S1PR1. FTY720 (fingolimod) was shown in 2002 to be phosphorylated in vivo and to act on four of the five S1P receptors. Two years later, lymphocyte egress from thymus and lymph nodes was found to depend on S1PR1. Ozanimod, BAF312 and ponesimod are further S1PR1-directed modulators, CYM 5442 HCl is a selective S1PR1 agonist and TY-52156 blocks S1PR3. Opaganib inhibits sphingosine kinase 2 (SphK2) and so limits S1P synthesis upstream of the receptors.
Synonyms: ABC-294640
ABC294640 is an orally available, aryladamantane compound and selective inhibitor of sphingosine kinase-2 (SK2) with potential antineoplastic activity.
Pro-FTY is a sphingosine-1-phosphate (S1P) inhibitor functioning as an anticancer prodrug derived from FTY720. It selectively disrupts S1P signaling in cancer cells using a drug delivery system that reacts with acrolein, demonstrating significant cytotoxic effects on breast cancer cells, including multidrug-resistant variants. Pro-FTY effectively suppresses tumor growth in xenograft models with 4T1 cells and organoids, while maintaining immune cell integrity by avoiding lymphocytopenia. This reagent is valuable for research in cancer therapy and resistance mechanisms.
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S118 is an orally active inhibitor of the sphingosine-1-phosphate receptor 2 (S1P2 receptor), which blocks the binding of Dpr1, subsequently reducing β-catenin accumulation. This mechanism inhibits nuclear translocation of the S1P2 receptor, contributing to the attenuation of inflammation, fibrosis, and epithelial-mesenchymal transition (EMT). S118 demonstrates potential for use in research related to idiopathic pulmonary fibrosis (IPF) and other fibrotic diseases.
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2-Acetyl-4-tetrahydroxybutyl imidazole is a potent inhibitor of sphingosine-1-phosphate (S1P) lyase, demonstrating significant biological activity in vivo. This compound is useful for investigating the role of S1P metabolism in various physiological and pathological processes. Research applications include studying cell signaling pathways and exploring therapeutic targets in diseases related to S1P dysregulation.
LX2931 is an inhibitor of Sphingosine 1-Phosphate Lyase (S1PL), which functions by elevating levels of Sphingosine 1-Phosphate (S1P) both intracellularly and extracellularly. This inhibition results in a marked increase in S1P concentrations in lymphoid tissues, potentially leading to restricted lymphocyte trafficking from secondary immune sites and contributing to lymphocytopenia and immunosuppressive effects in the peripheral circulation. LX2931 is valuable for research in autoimmune disease studies, particularly in the context of rheumatoid arthritis.
A6770 is a potent inhibitor of sphingosine 1-phosphate lyase (S1PL), an enzyme involved in sphingolipid metabolism. As an orally active compound, A6770 is phosphorylated to exert direct inhibitory effects on S1PL, leading to an increase in [3H]dhS1P levels. This reagent is valuable for research applications focused on sphingolipid signaling pathways and their roles in various biological processes.
RBM10-8 is an irreversible inhibitor of recombinant human sphingosine-1-phosphate lyase (hS1PL). This compound modulates the sphingosine-1-phosphate (S1P) signaling pathway, which plays a critical role in regulating various biological processes including cell proliferation, differentiation, angiogenesis, and immune responses. RBM10-8 is valuable for research applications focused on inflammation and developmental biology, providing insights into the therapeutic potential of targeting S1P-related pathways.
S1PL-IN-2 is a potent sphingosine-1-phosphate lyase (S1PL) inhibitor with an IC50 of 120 nM. It effectively inhibits S1PL activity by blocking the conversion of Vitamin B6 into the active cofactor pyridoxal-4-phosphate, which is essential for S1P lyase function. This compound is valuable for research in inflammation and immunology, with potential applications in studying conditions such as rheumatoid arthritis.
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