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Journal Article

Immunosuppressive effects of new thiophene-based KV1.3 inhibitors


Pardo,  Luis A.
Research Group of Oncophysiology, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

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Gubič, Š., Montalbano, A., Sala, C., Becchetti, A., Hendrickx, L. A., Theemsche, K. M. V., et al. (2023). Immunosuppressive effects of new thiophene-based KV1.3 inhibitors. European Journal of Medicinal Chemistry, 259: 115561. doi:10.1016/j.ejmech.2023.115561.

Cite as: https://hdl.handle.net/21.11116/0000-000D-751B-2
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.