Potassium channel blockers as immunosuppressants

Use of Kv1.3 Blockers for Inflammatory Skin Conditions

“…If we take as an example rat models of MS, chronic administration of ShK-186 was able to significantly reduce a set of key indicators for disease progression [109]. For a fuller discussion on the utility of Kv1.3 blockers in models of inflammation the following reviews are recommended [19,30,42,58]. For all researchers working in this field, a key transition is to successfully progress from animal models to properly conducted human clinical trials.…”

“…The following discussion provides a brief overview of each of the structural classes of small molecule Kv1.3 blockers highlighting the diversity of chemotypes and providing functional data where available. The reader is also directed to previous reviews on inhibitors of Kv1.3 channels in the following references [18,19,30,58]. This current review will primarily focus on series of compounds where SAR information is available.…”

Process Development and Optimization for Production of a Potassium Ion Channel Blocker, ICA-17043

“…Ion channels have emerged as attractive targets for the development of new therapies as they are implicated in the pathogenesis of several disease states, including vascular dysfunction, gastrointestinal dysmotility, memory disorders, neurological disorders, epilepsy, autoimmune and inflammatory diseases, to name a few. − In particular, the modulation of the intermediate conductance calcium-activated potassium ion channel, KCa3.1, a membrane protein found in lymphocytes, erythrocytes, fibroblasts, intestinal and airway epithelia, proliferating vascular smooth muscle, and vascular endothelium , offers avenues for potential pharmacological intervention, which can lead to the development of much needed therapies for several diseases. ICA-17043 is a selective and potent inhibitor of KCa3.1 for which a practical and scalable synthesis was required.…”