Špela Gubič (Author), Louise Antonia Hendrickx (Author), Xiaoyi Shi (Author), Žan Toplak (Author), Štefan Možina (Author), Kenny M. Van Theemsche (Author), Ernesto Lopes Pinheiro-Junior (Author), Steve Peigneur (Author), Tihomir Tomašić (Author), Lucija Peterlin-Mašič (Author)

Abstract

The voltage-gated potassium channel KV1.3 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 KV1.3 inhibitors through structural optimization of benzamide-based hit compounds and structure-activity relationship studies. The potency and selectivity of the new KV1.3 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 KV1.3 inhibitor 44 in the series with an IC50 value of 470 nM in oocytes and 950 nM in Ltk− cells. KV1.3 inhibitor 4 induced significant apoptosis in Colo-357 spheroids, while 14, 37, 43, and 44 significantly inhibited Panc-1 proliferation.

Keywords

Kv1.3;kalijevi ionski kanali;antiproliferativno delovanje;zdravila proti raku;potassium ion channels;antiproliferative activity;apoptosis;anticancer drugs;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FFA - Faculty of Pharmacy
UDC: 615.277.3:576.36
COBISS: 109409795 Link will open in a new window
ISSN: 2072-6694
Views: 32
Downloads: 6
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Metadata: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Other data

Secondary language: Slovenian
Secondary keywords: Rak (medicina);Apoptoza;Farmacevtska kemija;
Type (COBISS): Article
Pages: str. 1-20
Volume: ǂVol. ǂ14
Issue: ǂno. ǂ11, art. no. 2595
Chronology: 2022
DOI: 10.3390/cancers14112595
ID: 18572677