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Repurposing the K < sub > Ca < /sub > 3.1 Blocker Senicapoc for Ischemic Stroke
Transl Stroke Res. 2023 Apr 24. doi: 10.1007/s12975-023-01152-6. Online ahead of print.ABSTRACTSenicapoc, a small molecule inhibitor of the calcium-activated potassium channel KCa3.1, was safe and well-tolerated in clinical trials for sickle cell anemia. We previously reported proof-of-concept data suggesting that both pharmacological inhibition and genetic deletion of KCa3.1 reduces infarction and improves neurologic recovery in rodents by attenuating neuroinflammation. Here we evaluated the potential of repurposing senicapoc for ischemic stroke. In cultured microglia, senicapoc inhibited KCa3.1 currents with an IC50 of 7...
Source: Cell Research - April 24, 2023 Category: Cytology Authors: Ruth D Lee Yi-Je Chen Hai M Nguyen Latika Singh Connor J Dietrich Benjamin R Pyles Yanjun Cui Jonathan R Weinstein Heike Wulff Source Type: research

Repurposing the KCa3.1 Blocker Senicapoc for Ischemic Stroke
AbstractSenicapoc, a small molecule inhibitor of the calcium-activated potassium channel KCa3.1, was safe and well-tolerated in clinical trials for sickle cell anemia. We previously reported proof-of-concept data suggesting that both pharmacological inhibition and genetic deletion of KCa3.1 reduces infarction and improves neurologic recovery in rodents by attenuating neuroinflammation. Here we evaluated the potential of repurposing senicapoc for ischemic stroke. In cultured microglia, senicapoc inhibited KCa3.1 currents with an IC50 of 7  nM, reduced Ca2+ signaling induced by the purinergic agonist ATP, suppressed express...
Source: Translational Stroke Research - April 24, 2023 Category: Neurology Source Type: research