Store-Operated Calcium Entry as a Therapeutic Target in Acute Pancreatitis: Discovery and Development of Drug-Like SOCE Inhibitors

[Image: see text] Store-operated calcium entry (SOCE) is important in the maintenance of calcium homeostasis and alterations in this mechanism are responsible for several pathological conditions, including acute pancreatitis. Since the discovery of SOCE, many inhibitors have been identified and exte...

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Autores principales: Serafini, Marta, Cordero-Sanchez, Celia, Di Paola, Rosanna, Bhela, Irene P., Aprile, Silvio, Purghè, Beatrice, Fusco, Roberta, Cuzzocrea, Salvatore, Genazzani, Armando A., Riva, Beatrice, Pirali, Tracey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735735/
https://www.ncbi.nlm.nih.gov/pubmed/33253576
http://dx.doi.org/10.1021/acs.jmedchem.0c01305
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author Serafini, Marta
Cordero-Sanchez, Celia
Di Paola, Rosanna
Bhela, Irene P.
Aprile, Silvio
Purghè, Beatrice
Fusco, Roberta
Cuzzocrea, Salvatore
Genazzani, Armando A.
Riva, Beatrice
Pirali, Tracey
author_facet Serafini, Marta
Cordero-Sanchez, Celia
Di Paola, Rosanna
Bhela, Irene P.
Aprile, Silvio
Purghè, Beatrice
Fusco, Roberta
Cuzzocrea, Salvatore
Genazzani, Armando A.
Riva, Beatrice
Pirali, Tracey
author_sort Serafini, Marta
collection PubMed
description [Image: see text] Store-operated calcium entry (SOCE) is important in the maintenance of calcium homeostasis and alterations in this mechanism are responsible for several pathological conditions, including acute pancreatitis. Since the discovery of SOCE, many inhibitors have been identified and extensively used as chemical probes to better elucidate the role played by this cellular mechanism. Nevertheless, only a few have demonstrated drug-like properties so far. Here, we report a class of biphenyl triazoles among which stands out a lead compound, 34, that is endowed with an inhibitory activity at nanomolar concentrations, suitable pharmacokinetic properties, and in vivo efficacy in a mouse model of acute pancreatitis.
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spelling pubmed-77357352020-12-15 Store-Operated Calcium Entry as a Therapeutic Target in Acute Pancreatitis: Discovery and Development of Drug-Like SOCE Inhibitors Serafini, Marta Cordero-Sanchez, Celia Di Paola, Rosanna Bhela, Irene P. Aprile, Silvio Purghè, Beatrice Fusco, Roberta Cuzzocrea, Salvatore Genazzani, Armando A. Riva, Beatrice Pirali, Tracey J Med Chem [Image: see text] Store-operated calcium entry (SOCE) is important in the maintenance of calcium homeostasis and alterations in this mechanism are responsible for several pathological conditions, including acute pancreatitis. Since the discovery of SOCE, many inhibitors have been identified and extensively used as chemical probes to better elucidate the role played by this cellular mechanism. Nevertheless, only a few have demonstrated drug-like properties so far. Here, we report a class of biphenyl triazoles among which stands out a lead compound, 34, that is endowed with an inhibitory activity at nanomolar concentrations, suitable pharmacokinetic properties, and in vivo efficacy in a mouse model of acute pancreatitis. American Chemical Society 2020-11-30 2020-12-10 /pmc/articles/PMC7735735/ /pubmed/33253576 http://dx.doi.org/10.1021/acs.jmedchem.0c01305 Text en © 2020 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Serafini, Marta
Cordero-Sanchez, Celia
Di Paola, Rosanna
Bhela, Irene P.
Aprile, Silvio
Purghè, Beatrice
Fusco, Roberta
Cuzzocrea, Salvatore
Genazzani, Armando A.
Riva, Beatrice
Pirali, Tracey
Store-Operated Calcium Entry as a Therapeutic Target in Acute Pancreatitis: Discovery and Development of Drug-Like SOCE Inhibitors
title Store-Operated Calcium Entry as a Therapeutic Target in Acute Pancreatitis: Discovery and Development of Drug-Like SOCE Inhibitors
title_full Store-Operated Calcium Entry as a Therapeutic Target in Acute Pancreatitis: Discovery and Development of Drug-Like SOCE Inhibitors
title_fullStr Store-Operated Calcium Entry as a Therapeutic Target in Acute Pancreatitis: Discovery and Development of Drug-Like SOCE Inhibitors
title_full_unstemmed Store-Operated Calcium Entry as a Therapeutic Target in Acute Pancreatitis: Discovery and Development of Drug-Like SOCE Inhibitors
title_short Store-Operated Calcium Entry as a Therapeutic Target in Acute Pancreatitis: Discovery and Development of Drug-Like SOCE Inhibitors
title_sort store-operated calcium entry as a therapeutic target in acute pancreatitis: discovery and development of drug-like soce inhibitors
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735735/
https://www.ncbi.nlm.nih.gov/pubmed/33253576
http://dx.doi.org/10.1021/acs.jmedchem.0c01305
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