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

Marta Serafini; Celia Cordero-Sanchez; Rosanna Di Paola; Irene P. Bhela; Silvio Aprile; Beatrice Purghè; Roberta Fusco; Salvatore Cuzzocrea; Armando A. Genazzani; Beatrice Riva; Tracey Pirali

doi:10.1021/acs.jmedchem.0c01305

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

Marta Serafini
, Celia Cordero-Sanchez
, Rosanna Di Paola
, Irene P. Bhela
, Silvio Aprile
, Beatrice Purghè
, Roberta Fusco
, Salvatore Cuzzocrea
, Armando A. Genazzani
, Beatrice Riva
, Tracey Pirali

Dipartimento di Scienze del Farmaco

Risultato della ricerca: Contributo su rivista › Articolo in rivista › peer review

Abstract

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.

Lingua originale	Inglese
pagine (da-a)	14761-14779
Numero di pagine	19
Rivista	Journal of Medicinal Chemistry
Volume	63
Numero di pubblicazione	23
DOI	https://doi.org/10.1021/acs.jmedchem.0c01305
Stato di pubblicazione	Pubblicato - 10 dic 2020

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10.1021/acs.jmedchem.0c01305

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Serafini, M., Cordero-Sanchez, C., Di Paola, R., Bhela, I. P., Aprile, S., Purghè, B., Fusco, R., Cuzzocrea, S., Genazzani, A. A., Riva, B., & Pirali, T. (2020). Store-Operated Calcium Entry as a Therapeutic Target in Acute Pancreatitis: Discovery and Development of Drug-Like SOCE Inhibitors. Journal of Medicinal Chemistry, 63(23), 14761-14779. https://doi.org/10.1021/acs.jmedchem.0c01305

@article{3532fab93760448b8c8847b2b71750fb,

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

abstract = "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.",

author = "Marta Serafini and Celia Cordero-Sanchez and \{Di Paola\}, Rosanna and Bhela, \{Irene P.\} and Silvio Aprile and Beatrice Purgh{\`e} and Roberta Fusco and Salvatore Cuzzocrea and Genazzani, \{Armando A.\} and Beatrice Riva and Tracey Pirali",

note = "Publisher Copyright: {\textcopyright} 2020 American Chemical Society.",

year = "2020",

month = dec,

day = "10",

doi = "10.1021/acs.jmedchem.0c01305",

language = "English",

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Serafini, M, Cordero-Sanchez, C, Di Paola, R, Bhela, IP, Aprile, S, Purghè, B, Fusco, R, Cuzzocrea, S, Genazzani, AA, Riva, B & Pirali, T 2020, 'Store-Operated Calcium Entry as a Therapeutic Target in Acute Pancreatitis: Discovery and Development of Drug-Like SOCE Inhibitors', Journal of Medicinal Chemistry, vol. 63, n. 23, pagg. 14761-14779. https://doi.org/10.1021/acs.jmedchem.0c01305

TY - JOUR

T1 - Store-Operated Calcium Entry as a Therapeutic Target in Acute Pancreatitis

T2 - Discovery and Development of Drug-Like SOCE Inhibitors

AU - Serafini, Marta

AU - Cordero-Sanchez, Celia

AU - Di Paola, Rosanna

AU - Bhela, Irene P.

AU - Aprile, Silvio

AU - Purghè, Beatrice

AU - Fusco, Roberta

AU - Cuzzocrea, Salvatore

AU - Genazzani, Armando A.

AU - Riva, Beatrice

AU - Pirali, Tracey

PY - 2020/12/10

Y1 - 2020/12/10

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85097819870

U2 - 10.1021/acs.jmedchem.0c01305

DO - 10.1021/acs.jmedchem.0c01305

M3 - Article

SN - 0022-2623

VL - 63

SP - 14761

EP - 14779

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 23

ER -

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

Abstract

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