Dale Elena, Staal Roland G W, Eder Claudia, Möller Thomas
Neuroinflammation Disease Biology Unit, Lundbeck Research USA, Paramus, New Jersey.
Institute for Infection and Immunity, St. George's, University of London, United Kingdom.
Glia. 2016 Oct;64(10):1733-41. doi: 10.1002/glia.22992. Epub 2016 Apr 28.
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.
在过去十年中,胶质细胞因具有尚未开发的药物发现靶点而备受关注。正如本期《胶质细胞》特刊所强调的,几个胶质细胞靶点已经吸引了全新的药物发现项目。药物重新利用旨在将现有药物以及已放弃、失败或尚未进行临床开发的候选药物用于新的适应症,这可能会提供一个更快的机会,将针对胶质细胞靶点的药物带给有未满足需求的患者。在此,我们综述了中电导钙激活钾通道KCa 3.1作为这种重新利用努力靶点的潜力。我们讨论了KCa 3.1在体外和体内小胶质细胞上表达的数据,并综述了两种KCa 3.1抑制剂TRAM - 34和司尼卡波的相关文献。最后,我们展望了如何利用KCa 3.1作为真正的小胶质细胞药物靶点的潜力。《胶质细胞》2016年;64:1733 - 1741。