We describe a medicinal chemistry approach for generating a series of 2-(1H-pyrazol-1-yl)thiazoles as EP1 receptor antagonists. To improve the physicochemical properties of compound 1, we investigated its structure-activity relationships (SAR). Optimization of this lead compound provided small compound 25 which exhibited the best EP1 receptor antagonist activity and a good SAR profile.
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http://dx.doi.org/10.1016/j.bmcl.2013.10.065 | DOI Listing |
Fish Shellfish Immunol
December 2024
Liaoning Key Laboratory of Marine Animal Immunology and Disease Control, Dalian Ocean University, Dalian, 116023, China; Laboratory of Marine Fisheries Science and Food Production Process, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266235, China; Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, 116023, China; Dalian Key Laboratory of Aquatic Animal Disease Prevention and Control, Dalian Ocean University, Dalian, 116023, China.
Prostaglandin E2 imparts diverse physiological effects on multiple cells through its actions on four distinct E-type prostanoid (EP) receptor subtypes (EP1-EP4), among which the EP4 is one of subtypes known to mediate the immune response in mammalian monocytes and macrophages. However, the precise characteristics and functions of EP4 in mollusks remain unclear. In the present study, an EP4 homologue (designated as CgEP4) was identified from oyster Crassostrea gigas.
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 PDFJ Immunother Cancer
November 2024
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Background: Gastric carcinomas (GC) are aggressive malignancies, and only ~15% of patients respond to anti-programmed cell death (ligand) 1 (PD-(L)1) monotherapy. However, Epstein-Barr virus (EBV)-associated GCs (~5-10% of GCs) often harbor PD-L1 and PD-L2 chromosomal amplifications and robust CD8+ T cell infiltrates, and respond at a high rate to anti-PD-1. The current study compares the tumor immune microenvironments (TiMEs) of EBV+ versus EBV(-) GCs.
View Article and Find Full Text PDFVopr Pitan
November 2024
Federal Research Centre for Nutrition, Biotechnology and Food Safety, 109240, Moscow, Russian Federation.
The observed increase in the production of enzyme preparations (EP) using mutant and genetically modified microorganisms makes it necessary to assess their risks to consumer health. However, at present, their possible influence on the microbiome, immune status of the macroorganism has not been sufficiently studied. of the research was to assess the effect of two EP - the complex of hydrolases with proteolytic and nuclease activity from the Aspergillus oryzae RCAM 01134 mutant strain (EP1) and the neutral protease - bacillolysin and serine protease from the Bacillus subtilis-96 (VKM B-3499D) mutant strain (FP2) on the intestine microbiome and cellular immunity indices of the experimental animals.
View Article and Find Full Text PDFPharmaceuticals (Basel)
October 2024
Department of Physiology, Chosun University College of Medicine, Gwangju 61452, Republic of Korea.
Background: Prokinetic agents are effective in increasing gastrointestinal (GI) contractility and alleviating constipation, often caused by slow intestinal motility. Lubiprostone (LUB), known for activating CLC-2 chloride channels, increases the chloride ion concentration in the GI tract, supporting water retention and stool movement. Despite its therapeutic efficacy, the exact mechanisms underlying its pharmacological action are poorly understood.
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