A series of potent and selective EP(3) receptor antagonists are described. Utilizing a pharmacophore model developed for the EP(3) receptor, a series of 3,4-disubstituted indoles were found to be efficient ligands for this target. These compounds showed high selectivity over IP, FP and other EP receptors. An optimized molecule 7c featured a sound profile and potency in the functional rat and human platelet aggregation assays.
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http://dx.doi.org/10.1016/j.bmcl.2008.12.112 | DOI Listing |
Int J Mol Sci
December 2024
Department of Physiology and Cell Biology, School of Medicine, University of Nevada Reno, Reno, NV 89557, USA.
The urothelium and lamina propria (LP) contribute to sensations of bladder fullness by releasing multiple mediators, including prostaglandins (PGs) and adenosine 5'-triphosphate (ATP), that activate or modulate functions of cells throughout the bladder wall. Mediators that are simultaneously released in response to bladder distention likely influence each other's mechanisms of release and action. This study investigated whether PGs could alter the extracellular hydrolysis of ATP by soluble nucleotidases (s-NTDs) released in the LP of nondistended or distended bladders.
View Article and Find Full Text PDFDiagn Pathol
January 2025
Pathology Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277, Jiefang Avenue, Wuhan, 430022, Hubei Province, China.
Breast cancer became the most prevalent malignancy among women, and HER2 expression status is critical for treatment decisions. With the emergence of ADC drugs, HER2 low-expressing patients who previously did not respond well to traditional anti-HER2 therapies may now benefit. In this study, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were applied to assess HER2 expression in 349 patients with HER2-non-positive breast cancer.
View Article and Find Full Text PDFBiomedicines
December 2024
Department of Physiology, University of Murcia, 30120 Murcia, Spain.
Prostaglandins are naturally occurring local mediators that can participate in the modulation of the cardiovascular system through their interaction with Gs/Gi-coupled receptors in different tissues and cells, including platelets. Thrombin is one of the most important factors that regulates platelet reactivity and coagulation. Clinical trials have consistently shown that omega-3 fatty acid supplementation lowers the risk for cardiovascular mortality and morbidity.
View Article and Find Full Text PDFCell Signal
February 2025
Division of Cell Signalling and Immunology, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK. Electronic address:
The EP4 (prostaglandin E2) receptor plays a crucial role in myogenesis and skeletal muscle regeneration, yet its involvement in regulating insulin-dependent metabolic pathways is not well characterised. Our research investigates the expression of EP4 in rat skeletal L6 myotubes and its impact on insulin signalling. We found that activation of EP4 by selective agonists disrupts insulin signalling and insulin-stimulated glucose uptake.
View Article and Find Full Text PDFTemperature (Austin)
September 2024
Division of Neurobiology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Our body temperature is normally kept within a narrow range of 1°C. For example, if our body temperature rises, such as in a hot environment or due to strenuous exercise, our thermoregulatory system will trigger a powerful heat defense response with vasodilation, sweating, and lowered metabolism. During fever, which often involves body temperatures of up to 41°C, this heat defense mechanism is apparently inhibited; otherwise, the rising body temperature would be immediately combated, and fever would not be allowed to develop.
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