Immunosuppressive effects of new thiophene-based K$_V$1.3 inhibitorsGubič, Špela (Avtor) Ilaš, Janez (Avtor) Tomašič, Tihomir (Avtor) Arcangeli, Annarosa (Avtor) Peterlin-Mašič, Lucija (Avtor) ion channelK$_V$1.3 inhibitorT-lymphocyteimmunosuppressiveVoltage-gated potassium channel K$_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.20232023-11-10 09:08:53Članek v reviji152203sl