Immunosuppressive effects of new thiophene-based K V 1.3 inhibitors.

Voltage-gated potassium channel K _V 1.3 inhibitors have been shown to be effective in preventing T-cell proliferation and activation by affecting intracellular Ca ²⁺ homeostasis. Here, we present the structure-activity relationship, K _V 1.3 inhibition, and immunosuppressive effects of new thiophene-based K _V 1.3 inhibitors with nanomolar potency on K ⁺ current in T-lymphocytes and K _V 1.3 inhibition on Ltk ^- cells. The new K _V 1.3 inhibitor trans-18 inhibited K _V 1.3 -mediated current in phytohemagglutinin (PHA)-activated T-lymphocytes with an IC ₅₀ value of 26.1 nM and in mammalian Ltk ^- cells with an IC ₅₀ value of 230 nM. The K _V 1.3 inhibitor trans-18 also had nanomolar potency against K _V 1.3 in Xenopus laevis oocytes (IC ₅₀  = 136 nM). The novel thiophene-based K _V 1.3 inhibitors impaired intracellular Ca ²⁺ signaling as well as T-cell activation, proliferation, and colony formation.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)