20.500.12556/RUL-152203 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. ion channel K$_V$1.3 inhibitor T-lymphocyte immunosuppressive inhibitorji ionski kanal K$_V$1.3 T-limfocitni imunosupresiv ionski kanalčki imunosupresivna biološka zdravila true false true Angleški jezik Slovenski jezik Članek v reviji 2023-11-10 09:08:53 2023-11-10 09:08:55 2023-12-21 14:51:01 0000-00-00 00:00:00 2023 0 0 17 str. Vol. 259, art. 115561 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577.352:615.37 0223-5234 10.1016/j.ejmech.2023.115561 156924419 1-s2.0-S0223523423005275-main.pdf 1-s2.0-S0223523423005275-main.pdf 1 CA3B30AB98360DBAD8717D75BF572A8B e019e53744f6e623caf90efbe04fe9a6c51750956552792123be82a4ecb951c9 107b2bae-7fa9-11ee-bf5f-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=177548 https://www.sciencedirect.com/science/article/pii/S0223523423005275 1 64338dfb-7fa0-11ee-bf5f-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=177543 Fakulteta za farmacijo 0 0 0