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

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.