20.500.12556/RUL-145179 Design of new potent and selective thiophene-based K$_V$1.3 inhibitors and their potential for anticancer activity The voltage-gated potassium channel K$_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$1.3 inhibitor 4 induced significant apoptosis in Colo-357 spheroids, while 14, 37, 43, and 44 significantly inhibited Panc-1 proliferation. K$_V$1.3 potassium ion channels antiproliferative activity apoptosis anticancer drugs K$_V$1.3 kalijevi ionski kanali antiproliferativno delovanje zdravila proti raku rak apoptoza farmacevtska kemija true false true Angleški jezik Slovenski jezik Članek v reviji 2023-04-12 12:51:17 2023-04-12 12:51:20 2023-04-13 03:31:25 0000-00-00 00:00:00 2022 0 0 20 str. iss. 11, art. 2595 Vol. 14 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.277.3:576.36 2072-6694 10.3390/cancers14112595 109409795 cancers-14-02595-v3.pdf cancers-14-02595-v3.pdf 1 516D0CA34B37F5D1D523F3EF27BBB995 6afdb4c4e93d3d326aea8244de38be4e41ef6fe4c2e03b05f8dd34e8d59799f0 30b98d65-d920-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=167879 https://www.mdpi.com/2072-6694/14/11/2595 1 d063ea6e-d91f-11ed-a314-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=167878 Fakulteta za farmacijo 0 0 0