KCa 3.1-a microglial target ready for drug repurposing?
Over the past decade, glial cells have attracted attention for harboring unexploited targets for drug discovery. Several glial targets have attracted de novo drug discovery programs, as highlighted in this GLIA Special Issue. Drug repurposing, which has the objective of utilizing existing drugs as well as abandoned, failed, or not yet pursued clinical development candidates for new indications, might provide a faster opportunity to bring drugs for glial targets to patients with unmet needs. Here, we review the potential of the intermediate-conductance calcium-activated potassium channels KCa 3.1 as the target for such a repurposing effort. We discuss the data on KCa 3.1 expression on microglia in vitro and in vivo and review the relevant literature on the two KCa 3.1 inhibitors TRAM-34 and Senicapoc. Finally, we provide an outlook of what it might take to harness the potential of KCa 3.1 as a bona fide microglial drug target. GLIA 2016;64:1733-1741.
Neuroinflammation Disease Biology Unit, Lundbeck Research USA, Paramus, New Jersey.
Elena
E
Dale
Neuroinflammation Disease Biology Unit, Lundbeck Research USA, Paramus, New Jersey.
Roland G W
RG
Staal
Institute for Infection and Immunity, St. George's, University of London, United Kingdom.
Claudia
C
Eder
Neuroinflammation Disease Biology Unit, Lundbeck Research USA, Paramus, New Jersey.
Thomas
T
Möller
D000081:Acetamides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D058492:Drug Repositioning; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014320:Triphenylmethyl Compounds / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
D000081:Acetamides; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D011720:Pyrazoles; C411671:TRAM 34; D014320:Triphenylmethyl Compounds; C472774:senicapoc
KCa3.1; NCATS; drug repurposing; drug target; microglia