Blog
About

  • Record: found
  • Abstract: found
  • Poster: not found
Is Open Access

Kv1.3 inhibitors: en route to clinical trials

ScienceOpen Posters

ScienceOpen

This work has been published open access under Creative Commons Attribution License CC BY 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com.

autoimmune diseases, Kv1.3 inhibitors, selective immunosuppression, autoreactive T-cells

Read this article at

ScienceOpen
Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      The voltage-gated potassium channel Kv1.3 represents a promising target for the treatment of autoimmune diseases like multiple sclerosis, rheumatoid arthritis, uveitis and psoriasis as it is a crucial player in maintaining the activation signal within T-cells, allowing for a selective suppression of autoimmunity and thus minimizing the potential for opportunistic infections during therapy. The Lead Optimization Program for two small molecule hit classes resulted in a fine-tuning of activity, selectivity and physicochemical and PK properties. Selected representatives display highly encouraging ameliorative effects within a set of animal models relevant in the context of autoimmune diseases, comparable or even favourable over positive controls like methotrexate, betamethasone or tacrolimus. Such inhibitors showed excellent tolerability in rats upon oral treatment with high doses for up to a month, had no effect on haematology and clinical biochemistry parameters and did not affect cells of the innate immunity or naive T-cells, clearly emphasizing their unique selling point, which is a highly specific immunosuppression of autoreactive T-cells.

      Related collections

      Author and article information

      Journal
      10.14293/P2199-8442.1.SOP-CHEM.PDKXFG.v1

      Comments

      Comment on this article