Design of new potent and selective thiophene-based K$_V$1.3 inhibitors and their potential for anticancer activity

Gubič, Špela (avtor), Toplak, Žan (avtor), Možina, Štefan (avtor), Tomašič, Tihomir (avtor), Peterlin-Mašič, Lucija (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: K$_V$1.3, potassium ion channels, antiproliferative activity, apoptosis, anticancer drugs
• 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: 2022
• Št. strani: 20 str.
• Številčenje: Vol. 14, iss. 11, art. 2595
• PID: 20.500.12556/RUL-145179
• UDK: 615.277.3:576.36
• ISSN pri članku: 2072-6694
• DOI: 10.3390/cancers14112595
• COBISS.SI-ID: 109409795
• Datum objave v RUL: 12.04.2023

Gradivo je del revije

• Naslov: Cancers
• Skrajšan naslov: Cancers
• Založnik: MDPI
• ISSN: 2072-6694
• COBISS.SI-ID: 517914137

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: K$_V$1.3, kalijevi ionski kanali, antiproliferativno delovanje, zdravila proti raku, rak, apoptoza, farmacevtska kemija