ArticleJournal of lipid research2014
Inhibition of dihydroceramide desaturase activity by the sphingosine kinase inhibitor SKI II.
Article in Journal of lipid research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 77 citations in OpenAlex.
- Genome-wide identification of modulators of Chlamydia trachomatis parasitophorous vacuole stability highlights an important role for sphingolipid supply.PLoS biology · 2025Article
- Targeting sphingolipid metabolism in chronic lymphocytic leukemia.Clinical and experimental medicine · 2024Article
- Fanning the Flames of Endoplasmic Reticulum (ER) Stress: Can Sphingolipid Metabolism Be Targeted to Enhance ER Stress-Associated Immunogenic Cell Death in Cancer?Molecular pharmacology · 2024Review
- Targeting the SphK1/S1P/PFKFB3 axis suppresses hepatocellular carcinoma progression by disrupting glycolytic energy supply that drives tumor angiogenesis.Journal of translational medicine · 2024Article
- The role of sphingolipid rheostat in the adult-type diffuse glioma pathogenesis.Frontiers in cell and developmental biology · 2024Review
- Integrative roles of sphingosine kinase in liver pathophysiology.Toxicological research · 2023Review
- Article
- Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology.Frontiers in physiology · 2023Review
- Dihydroceramide desaturase 1 (DES1) promotes anchorage-independent survival downstream of HER2-driven glucose uptake and metabolism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Targeting the Sphingolipid Rheostat in Gliomas.International journal of molecular sciences · 2022Review
- Very-Long-Chain Unsaturated Sphingolipids Mediate Oleate-Induced Rat β-Cell Proliferation.Diabetes · 2022Article
- The sphingosine 1-phosphate receptor 2/4 antagonist JTE-013 elicits off-target effects on sphingolipid metabolism.Scientific reports · 2022Article
- Diets with Higher ω-6/ω-3 Ratios Show Differences in Ceramides and Fatty Acid Levels Accompanied by Increased Amyloid-Beta in the Brains of Male APP/PS1 Transgenic Mice.International journal of molecular sciences · 2021Article
- A Dansyl-Modified Sphingosine Kinase Inhibitor DPF-543 Enhanced De Novo Ceramide Generation.International journal of molecular sciences · 2021Article
- Small Molecule Inhibitors Targeting Biosynthesis of Ceramide, the Central Hub of the Sphingolipid Network.Journal of medicinal chemistry · 2021Review
- Therapeutic Potential of SphK1 Inhibitors Based on Abnormal Expression of SphK1 in Inflammatory Immune Related-Diseases.Frontiers in pharmacology · 2021Review
- Sphingosine Kinase 1 Signaling in Breast Cancer: A Potential Target to Tackle Breast Cancer Stem Cells.Frontiers in molecular biosciences · 2021Review
- A Novel Selective Sphingosine Kinase 2 Inhibitor, HWG-35D, Ameliorates the Severity of Imiquimod-Induced Psoriasis Model by Blocking Th17 Differentiation of Naïve CD4 T Lymphocytes.International journal of molecular sciences · 2020Article
- Analysis of selective target engagement by small-molecule sphingosine kinase inhibitors using the Cellular Thermal Shift Assay (CETSA).Cancer biology & therapy · 2020Article
- Druggable Sphingolipid Pathways: Experimental Models and Clinical Opportunities.Advances in experimental medicine and biology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingosine kinase inhibitor (SKI) II has been reported as a dual inhibitor of sphingosine kinases (SKs) 1 and 2 and has been extensively used to prove the involvement of SKs and sphingosine-1-phosphate (S1P) in cellular processes. Dihydroceramide desaturase (Des1), the last enzyme in the de novo synthesis of ceramide (Cer), regulates the balance between dihydroceramides (dhCers) and Cers. Both SKs and Des1 have interest as therapeutic targets. Here we show that SKI II is a noncompetitive inhibitor (Ki = 0.3 μM) of Des1 activity with effect also in intact cells without modifying Des1 protein levels. Molecular modeling studies support that the SKI II-induced decrease in Des1 activity could result from inhibition of NADH-cytochrome b5 reductase. SKI II, but not the SK1-specific inhibitor PF-543, provoked a remarkable accumulation of dhCers and their metabolites, while both SKI II and PF-543 reduced S1P to almost undetectable levels. SKI II, but not PF543, reduced cell proliferation with accumulation of cells in the G0/G1 phase. SKI II, but not PF543, induced autophagy. These overall findings should be taken into account when using SKI II as a pharmacological tool, as some of the effects attributed to decreased S1P may actually be caused by augmented dhCers and/or their metabolites.
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Registered trials
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.