title: Senicapoc: Repurposing a Drug to Target Microglia KCa3.1 in Stroke.
abstract: Stroke is the leading cause of serious long-term disability and the fifth leading cause of death in the United States. Treatment options for stroke are few in number and limited in efficacy. Neuroinflammation mediated by microglia and infiltrating peripheral immune cells is a major component of stroke pathophysiology. Interfering with the inflammation cascade after stroke holds the promise to modulate stroke outcome. The calcium activated potassium channel KCa3.1 is expressed selectively in the injured CNS by microglia. KCa3.1 function has been implicated in pro-inflammatory activation of microglia and there is recent literature suggesting that this channel is important in the pathophysiology of ischemia/reperfusion (stroke) related brain injury. Here we describe the potential of repurposing Senicapoc, a KCa3.1 inhibitor, to intervene in the inflammation cascade that follows ischemia/reperfusion.
authors.affiliation: Alentis Pharma LLC, 72 Hillside Avenue, Metuchen, NJ, 08840, USA.
authors.forename: Roland G W
authors.initials: RGW
authors.lastname: Staal
authors.affiliation: Department of Neurology, School of Medicine, University of Washington, Seattle, WA, 98195, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Weinstein
authors.affiliation: Neuroinflammation Disease Biology Unit, Lundbeck Research USA Inc., 215 College Rd, Paramus, NJ, 07652, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Nattini
authors.affiliation: Neuroinflammation Disease Biology Unit, Lundbeck Research USA Inc., 215 College Rd, Paramus, NJ, 07652, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Cajina
authors.affiliation: Neuroinflammation Disease Biology Unit, Lundbeck Research USA Inc., 215 College Rd, Paramus, NJ, 07652, USA.
authors.forename: Gamini
authors.initials: G
authors.lastname: Chandresana
authors.affiliation: Abbvie, Foundational Neuroscience Center, Cambridge, MA, 02139, USA. thomas.moeller@abbvie.com.
authors.forename: Thomas
authors.identifier: http://orcid.org/0000-0003-3671-5684
authors.initials: T
authors.lastname: Möller
mesh_terms: D000081:Acetamides / Q000008:administration & dosage*; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D058492:Drug Repositioning / Q000379:methods*; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D011720:Pyrazoles / Q000008:administration & dosage; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism*; D014320:Triphenylmethyl Compounds / Q000008:administration & dosage*
chemical_list: D000081:Acetamides; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D011720:Pyrazoles; C411671:TRAM 34; D014320:Triphenylmethyl Compounds; C472774:senicapoc
keywords: Drug repurposing; Ischemia; Microglia; Neuroinflammation; Stroke