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Development Of A Selective Inhibitor For Kv1.1 Channels Prevalent In Demyelinated Nerves, Ahmed Al-Sabi, Declan Daly, Myles Rooney, Cian Hughes, Gemma K. Kinsella, Seshu Kaza, Kieran Nolan, J. Oliver Dolly
Development Of A Selective Inhibitor For Kv1.1 Channels Prevalent In Demyelinated Nerves, Ahmed Al-Sabi, Declan Daly, Myles Rooney, Cian Hughes, Gemma K. Kinsella, Seshu Kaza, Kieran Nolan, J. Oliver Dolly
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Members of the voltage-gated K+ channel subfamily (Kv1), involved in regulating transmission between neurons or to muscles, are associated with human diseases and, thus, putative targets for neurotherapeutics. This applies especially to those containing Kv1.1 α subunits which become prevalent in murine demyelinated axons and appear abnormally at inter-nodes, underlying the perturbed propagation of nerve signals. To overcome this dysfunction, akin to the consequential debilitation in multiple sclerosis (MS), small inhibitors were sought that are selective for the culpable hyper-polarising K+ currents. Herein, we report a new semi-podand – compound 3 – that was designed based on the modelling of …