Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 9 of 9 for “"SPHK2"”.
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The Role of Sphingosine Kinase 2 in Cell Growth and Apoptosis
… when overexpressed in mouse NIH 3T3 fibroblasts SphK2 enhances caspase-dependent apoptosis in response to serum deprivation, independently of S1P receptors. Sequence analysis revealed that SphK2 contains a 9 amino acid motif similar to that present in BH3-only proteins. Studies showed that the …
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Design and Synthesis of Orally Bioavailable Sphingosine Kinase 2 Selective Inhibitors
… enzyme's sphingosine kinase 1 and 2 (SphK1 and SphK2). Inhibition of SphK1 and SphK2 results in the manipulation of S1P levels, which has been shown to be therapeutic in various animal models of disease. While there are multiple examples of potent SphK1-selective and dual SphK1/2 inhibitors, …
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Structure Activity Relationship Studies on Isoform Selective Sphingosine Kinase Inhibitors
… two isoforms of sphingosine kinase (SphK1 and SphK2). Therefore, SphKs are a potential therapeutic target; however, the physiological role of SphK2 is still emerging. In order to determine the role of SphK2 in vivo, more potent and selective small molecule inhibitors of SphK2, as well as dual …
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Structure-activity relationship studies and biological evaluation of selective sphingosine kinase inhibitors
… the structure-activity relationships (SAR) of SphK2 through an iterative process of synthesis and biological testing. First, an SAR structured around the head and linker region of our lead molecule, SLR080811, was performed. SLR080811 has a Ki of 1.3 µM and is 5-fold selective for SphK2. The …
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Structure-Activity Relationship Studies of Sphingosine Kinase Inhibitors and Mitochondrial Uncouplers
… and SphK exists as two isoforms-"SphK1 and SphK2, which differ with respect to their cellular activity and localization. As the key mediators in the synthesis of S1P, SphKs have attracted attention as viable targets for pharmaceutical inhibition. To validate their potential as therapeutic …
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Design, synthesis, and biological evaluation of selective sphingosine kinase inhibitors
… as two different isoforms, namely SphK1 and SphK2, which play different roles inside the cell. The dearth of isoenzyme-selective inhibitors has been a stumbling block for probing the exact roles of these two isoforms in disease progression. This report documents our efforts in developing …
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Identification of Familial Wilms Tumor Predisposition Genes Using Whole Genome Sequencing
… in <em>DICER1 </em>(4% of families) and <em>SPHK2</em>. Functional studies demonstrate that the missense mutation identified in <em>SPHK2 </em>does not have an effect on apoptosis or proliferation, but instead alters SPHK2 subcellular localization and expression of target genes.</p> <p>Our …
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Cell-Type Specific Translational Profiling in Huntington's Disease Mouse Models
… We have preliminary evidence to suggest Sphk2 and Sgpl1, the enzymes responsible for the production and degradation of S1P, are altered in HD mouse models in patterns that might explain the changes in S1P levels. We have shown that S1P can have pro-survival effects in an in vitro model of …
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Rol de los esfingolípidos en los procesos activados por estrés oxidativo en neuronas y células gliales de retina
… de las cuales se conocen dos isoformas, SphK1 y SphK2. Con diversas técnicas citoquímicas, determinamos que DHA protege a los fotorreceptores de la apoptosis por daño oxidativo o por agregado de ceramida o esfingosina, y que la inhibición de la formación de S1P, catalizada por la SphK1 bloquea el …