ArticleThe Journal of pharmacology and experimental therapeutics2015
Sphingosine Kinase 2 Inhibition and Blood Sphingosine 1-Phosphate Levels.
Article in The Journal of pharmacology and experimental therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 65 citations in OpenAlex.
- The emerging roles of sphingosine 1-phosphate and SphK1 in cancer resistance: a promising therapeutic target.Cancer cell international · 2024Review
- Sphingosine kinase 1/S1P receptor signaling axis is essential for cellular uptake of Neisseria meningitidis in brain endothelial cells.PLoS pathogens · 2023Article
- Integrative roles of sphingosine kinase in liver pathophysiology.Toxicological research · 2023Review
- Natural Products and Small Molecules Targeting Cellular Ceramide Metabolism to Enhance Apoptosis in Cancer Cells.Cancers · 2023Review
- Assay of Sphingosine 1-phosphate Transporter Spinster Homolog 2 (Spns2) Inhibitors.SLAS discovery : advancing life sciences R & D · 2023Article
- Adiponectin Modulates Smooth Muscle Cell Morpho-Functional Properties in Murine Gastric Fundus via Sphingosine Kinase 2 Activation.Life (Basel, Switzerland) · 2023Article
- Sphingosine Kinases at the Intersection of Pro-Inflammatory LPS and Anti-Inflammatory Endocannabinoid Signaling in BV2 Mouse Microglia Cells.International journal of molecular sciences · 2023Article
- Sphingosine Kinase 2 in Stromal Fibroblasts Creates a Hospitable Tumor Microenvironment in Breast Cancer.Cancer research · 2023Article
- FTY720 Reduces Lipid Accumulation by Upregulating ABCA1 through Liver X Receptor and Sphingosine Kinase 2 Signaling in Macrophages.International journal of molecular sciences · 2022Article
- Ablation of sphingosine kinase 2 suppresses fatty liver-associated hepatocellular carcinoma via downregulation of ceramide transfer protein.Oncogenesis · 2022Article
- Sphingosine Kinase 2 Inhibitors: Rigid Aliphatic Tail Derivatives Deliver Potent and Selective Analogues.ACS bio & med chem Au · 2022Article
- Sphingosine 1-phosphate receptor-targeted therapeutics in rheumatic diseases.Nature reviews. Rheumatology · 2022Review
- Article
- Sphk1 and Sphk2 Differentially Regulate Erythropoietin Synthesis in Mouse Renal Interstitial Fibroblast-like Cells.International journal of molecular sciences · 2022Article
- Sphk2 deletion is involved in structural abnormalities and Th17 response but does not aggravate colon inflammation induced by sub-chronic stress.Scientific reports · 2022Article
- Sphingosine-1-phosphate modulates PAR1-mediated human platelet activation in a concentration-dependent biphasic manner.Scientific reports · 2021Article
- Probing the substitution pattern of indole-based scaffold reveals potent and selective sphingosine kinase 2 inhibitors.European journal of medicinal chemistry · 2021Article
- Lipophilic tail modifications of 2-(hydroxymethyl)pyrrolidine scaffold reveal dual sphingosine kinase 1 and 2 inhibitors.Bioorganic & medicinal chemistry · 2021Article
- Structure-activity relationship studies and bioactivity evaluation of 1,2,3-triazole containing analogues as a selective sphingosine kinase-2 inhibitors.European journal of medicinal chemistry · 2020Article
- Targeting the SphK-S1P-SIPR Pathway as a Potential Therapeutic Approach for COVID-19.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Sphingosine 1-phosphate (S1P) levels are significantly higher in blood and lymph than in tissues. This S1P concentration difference is necessary for proper lymphocyte egress from secondary lymphoid tissue and to maintain endothelial barrier integrity. Studies with mice lacking either sphingosine kinase (SphK) type 1 and 2 indicate that these enzymes are the sole biosynthetic source of S1P, but they play different roles in setting S1P blood levels. We have developed a set of drug-like SphK inhibitors, with differing selectivity for the two isoforms of this enzyme. Although all SphK inhibitors tested decrease S1P when applied to cultured U937 cells, only those inhibitors with a bias for SphK2 drove a substantial increase in blood S1P in mice and this rise was detectable within minutes of administration of the inhibitor. Blood S1P also increased in response to SphK2 inhibitors in rats. Mass-labeled S1P was cleared more slowly after intravenous injection into SphK2 inhibitor-treated mice or mice lacking a functional SphK2 gene; thus, the increased accumulation of S1P in the blood appears to result from the decreased clearance of S1P from the blood. Therefore, SphK2 appears to have a function independent of generating S1P in cells. Our results suggest that differential SphK inhibition with a drug might afford a method to manipulate blood S1P levels in either direction while lowering tissue S1P levels.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.