Repurposing the K_Ca3.1 Blocker Senicapoc for Ischemic Stroke.

ABSTRACT: Senicapoc, 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 expression of pro-inflammatory cytokines and enzymes (iNOS and COX-2), and prevented induction of the inflammasome component NLRP3. When transient middle cerebral ar

SUBMITTER: Lee RD 

PROVIDER: S-EPMC11106165 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature