Immunosuppressive effects of new thiophene-based K$_V$1.3 inhibitors

Gubič, Špela (avtor), Ilaš, Janez (avtor), Tomašič, Tihomir (avtor), Arcangeli, Annarosa (avtor), Peterlin-Mašič, Lucija (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: ion channel, K$_V$1.3 inhibitor, T-lymphocyte, immunosuppressive
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2023
• Št. strani: 17 str.
• Številčenje: Vol. 259, art. 115561
• PID: 20.500.12556/RUL-152203
• UDK: 577.352:615.37
• ISSN pri članku: 0223-5234
• DOI: 10.1016/j.ejmech.2023.115561
• COBISS.SI-ID: 156924419
• Datum objave v RUL: 10.11.2023

Gradivo je del revije

• Naslov: European journal of medicinal chemistry
• Skrajšan naslov: Eur. j. med. chem.
• Založnik: Elsevier
• ISSN: 0223-5234
• COBISS.SI-ID: 25429760

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: inhibitorji, ionski kanal K$_V$1.3, T-limfocitni imunosupresiv, ionski kanalčki, imunosupresivna biološka zdravila