1,345
views
0
recommends
+1 Recommend
1 collections
    53
    shares

      Publish your conference poster on ScienceOpen Posters to carry on the conversation.

      All posters are assigned an Open Access CC BY 4.0 license, a Crossref DOI and are integrated with ORCID, ROR, FunderID and more for best discoverability.

      scite_
       
      • Record: found
      • Abstract: found
      • Poster: found
      Is Open Access

      Kv1.3 inhibitors: en route to clinical trials

      Published
      poster
        , , ,
      ScienceOpen Posters
      ScienceOpen
      248th ACS National Meeting
      Kv1.3 inhibitors, selective immunosuppression, autoreactive T-cells, autoimmune diseases
      Bookmark

            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.

            Content

            Author and article information

            Conference
            ScienceOpen Posters
            ScienceOpen
            September 29 2014
            Author information
            https://orcid.org/0000-0002-2718-8432
            Article
            10.14293/P2199-8442.1.SOP-CHEM.PDKXFG.v1
            0c075664-abf8-415c-a66b-63721e0755cb

            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 .

            248th ACS National Meeting
            History

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

            Comments

            Comment on this article