Pyrtriazoles, a Novel Class of Store-Operated Calcium Entry Modulators: Discovery, Biological Profiling, and in Vivo Proof-of-Concept Efficacy in Acute PancreatitisClick to copy article linkArticle link copied!
- Beatrice RivaBeatrice RivaDepartment of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara 28100, ItalyChemICare Srl, Enne3, Novara 28100, ItalyMore by Beatrice Riva
- Alessia GriglioAlessia GriglioDepartment of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara 28100, ItalyMore by Alessia Griglio
- Marta SerafiniMarta SerafiniDepartment of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara 28100, ItalyMore by Marta Serafini
- Celia Cordero-SanchezCelia Cordero-SanchezDepartment of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara 28100, ItalyMore by Celia Cordero-Sanchez
- Silvio AprileSilvio AprileDepartment of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara 28100, ItalyMore by Silvio Aprile
- Rosanna Di PaolaRosanna Di PaolaDepartment of Chemical, Biological, Pharmaceutical, and Enviromental Sciences, Università di Messina, Messina 98166, ItalyMore by Rosanna Di Paola
- Enrico GugliandoloEnrico GugliandoloDepartment of Chemical, Biological, Pharmaceutical, and Enviromental Sciences, Università di Messina, Messina 98166, ItalyMore by Enrico Gugliandolo
- Dalia AlansaryDalia AlansaryDepartment of Molecular Biophysics, Saarland University CIPMM, Homburg 66421, GermanyMore by Dalia Alansary
- Isabella BiocotinoIsabella BiocotinoDepartment of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara 28100, ItalyMore by Isabella Biocotino
- Dmitry LimDmitry LimDepartment of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara 28100, ItalyMore by Dmitry Lim
- Giorgio GrosaGiorgio GrosaDepartment of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara 28100, ItalyMore by Giorgio Grosa
- Ubaldina GalliUbaldina GalliDepartment of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara 28100, ItalyMore by Ubaldina Galli
- Barbara NiemeyerBarbara NiemeyerDepartment of Molecular Biophysics, Saarland University CIPMM, Homburg 66421, GermanyMore by Barbara Niemeyer
- Giovanni SorbaGiovanni SorbaDepartment of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara 28100, ItalyMore by Giovanni Sorba
- Pier Luigi CanonicoPier Luigi CanonicoDepartment of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara 28100, ItalyMore by Pier Luigi Canonico
- Salvatore CuzzocreaSalvatore CuzzocreaDepartment of Chemical, Biological, Pharmaceutical, and Enviromental Sciences, Università di Messina, Messina 98166, ItalyMore by Salvatore Cuzzocrea
- Armando A. GenazzaniArmando A. GenazzaniDepartment of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara 28100, ItalyMore by Armando A. Genazzani
- Tracey Pirali*Tracey Pirali*Phone: 0039-0321-375852. Fax: 0039-0321-375821. E-mail: [email protected]. Address: Department of Pharmaceutical Sciences, Università del Piemonte Orientale, Largo Donegani 2, 28100 Novara, Italy.Department of Pharmaceutical Sciences, Università del Piemonte Orientale, Novara 28100, ItalyChemICare Srl, Enne3, Novara 28100, ItalyMore by Tracey Pirali
Abstract
In recent years, channels that mediate store-operated calcium entry (SOCE, i.e., the ability of cells to sense a decrease in endoplasmic reticulum luminal calcium and induce calcium entry across the plasma membrane) have been associated with a number of disorders, spanning from immune disorders to acute pancreatitis and have been suggested to be druggable targets. In the present contribution, we exploited the click chemistry approach to synthesize a class of SOCE modulators where the arylamide substructure that characterizes most inhibitors so far described is substituted by a 1,4-disubstituted 1,2,3-triazole ring. Within this series, inhibitors of SOCE were identified and the best compound proved effective in an animal model of acute pancreatitis, a disease characterized by a hyperactivation of SOCE. Strikingly, two enhancers of the process were discovered, affording invaluable research tools to further explore the (patho)physiological role of capacitative calcium entry.
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