Immunosuppressive effects of new thiophene-based KV1.3 inhibitors

卷:259

Article

关键词: GATED POTASSIUM CHANNEL;    MEMORY T-CELLS;    K+ CHANNELS;    ION CHANNELS;    PAP-1;    LYMPHOCYTES;    MECHANISM;    BLOCKERS;    K(V)1.3;    DESIGN;   

DOI  :  10.1016/j.ejmech.2023.115561

来源: SCIE

【 摘 要 】

Voltage-gated potassium channel KV1.3 inhibitors have been shown to be effective in preventing T-cell proliferation and activation by affecting intracellular Ca2+ homeostasis. Here, we present the structure-activity relationship, KV1.3 inhibition, and immunosuppressive effects of new thiophene-based KV1.3 inhibitors with nanomolar potency on K+ current in T-lymphocytes and KV1.3 inhibition on Ltk- cells. The new KV1.3 inhibitor trans -18 inhibited KV1.3-mediated current in phytohemagglutinin (PHA)-activated T-lymphocytes with an IC50 value of 26.1 nM and in mammalian Ltk- cells with an IC50 value of 230 nM. The KV1.3 inhibitor trans -18 also had nanomolar potency against KV1.3 in Xenopus laevis oocytes (IC50 = 136 nM). The novel thiophene-based KV1.3 inhibitors impaired intracellular Ca2+ signaling as well as T-cell activation, proliferation, and colony formation.

【 授权许可】

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