Sphingosine kinases (SK1 and SK2) are key, druggable targets within the sphingolipid metabolism pathway that promote tumor growth and pathologic inflammation. A variety of isozyme-selective and dual inhibitors of SK1 and SK2 have been described in the literature, and at least one compound has reached clinical testing in cancer patients. In this chapter, we will review the rationale for targeting SKs and summarize the preclinical and emerging clinical data for ABC294640 as the first-in-class selective inhibitor of SK2.
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http://dx.doi.org/10.1016/bs.acr.2018.04.015 | DOI Listing |
Inn Med (Heidelb)
January 2025
Abteilung für interventionelle gastroenterologische Endoskopie, Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland.
Background: In chronic inflammatory bowel diseases (IBD), severe flares are characterized by intense inflammatory activity and a high disease burden for patients. Treatment addresses both short-term goals (e.g.
View Article and Find Full Text PDFJ Virol
January 2025
Microbiology and Immunology, Carver College of Medicine, The University of Iowa, Iowa City, Iowa, USA.
Measles virus (MeV) is a highly contagious respiratory virus transmitted via aerosols. To understand how MeV exits the airways of an infected host, we use unpassaged primary cultures of human airway epithelial cells (HAE). MeV typically remains cell-associated in HAE and forms foci of infection, termed infectious centers, by directly spreading cell-to-cell.
View Article and Find Full Text PDFEur J Nutr
January 2025
College of Pharmacy, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, China.
Background: Severe disruption of lipid metabolism in vivo is one of the central mechanisms in the development of atherosclerotic vascular injury (AVI). Reverse cholesterol transport (RCT) plays a pivotal role in eliminating excess cholesterol, preventing lipid deposition in the aorta, and reducing plaque formation associated with AVI. Floralozone (FL) reduces endothelial cell injury in AVI rats by regulating sphingosine-1-phosphate (S1P) expression.
View Article and Find Full Text PDFHepatol Commun
December 2024
Department of Microbiology and Immunology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
Background: Sphingosine-1 phosphate (S1P) is a bioactive lipid molecule that modulates inflammation and hepatic lipid metabolism in MASLD, which affects 1 in 3 people and increases the risk of liver fibrosis and hepatic cancer. S1P can be generated by 2 isoforms of sphingosine kinase (SphK). SphK1 is well-studied in metabolic diseases.
View Article and Find Full Text PDFPharmaceuticals (Basel)
November 2024
Department of Medical Biochemistry, Faculty of Medicine, Akdeniz University, Antalya 07070, Turkey.
The aim of this study was to determine the effect of Sparstolonin B (SsnB) on cell proliferation and apoptosis in human breast cancer (MCF-7) and human ovarian epithelial cancer (OVCAR-3) cell lines in the presence and absence of estradiol hemihydrate (ES). Phosphoinositol-3 kinase (PI3K), phosphorylated protein kinase B alpha (p-AKT), phosphorylated mTOR (mechanistic target of rapamycin) signaling proteins, and sphingomyelin/ceramide metabolites were also measured within the scope of the study. The anti-proliferative effects of SsnB therapy were evaluated over a range of times and concentrations.
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