Design of new potent and selective thiophene-based K$_V$1.3 inhibitors and their potential for anticancer activityGubič, Špela (Avtor) Toplak, Žan (Avtor) Možina, Štefan (Avtor) Tomašič, Tihomir (Avtor) Peterlin-Mašič, Lucija (Avtor) K$_V$1.3potassium ion channelsantiproliferative activityapoptosisanticancer drugsThe voltage-gated potassium channel K$_V$1.3 has been recognized as a tumor marker and represents a promising new target for the discovery of new anticancer drugs. We designed a novel structural class of K$_V$1.3 inhibitors through structural optimization of benzamide-based hit compounds and structure-activity relationship studies. The potency and selectivity of the new K$_V$1.3 inhibitors were investigated using whole-cell patch- and voltage-clamp experiments. 2D and 3D cell models were used to determine antiproliferative activity. Structural optimization resulted in the most potent and selective K$_V$1.3 inhibitor 44 in the series with an IC$_{50}$ value of 470 nM in oocytes and 950 nM in Ltk$^−$ cells. K$_V$1.3 inhibitor 4 induced significant apoptosis in Colo-357 spheroids, while 14, 37, 43, and 44 significantly inhibited Panc-1 proliferation.20222023-04-12 12:51:17Članek v reviji145179sl