Špela Gubič (Author), Alberto Montalbano (Author), Cesare Sala (Author), Andrea Becchetti (Author), Louise Antonia Hendrickx (Author), Kenny M. Van Theemsche (Author), Ernesto Lopes Pinheiro-Junior (Author), Janez Ilaš (Author), Tihomir Tomašić (Author), Lucija Peterlin-Mašič (Author)

Abstract

Voltage-gated potassium channel KV1.3 inhibitors have been shown to be effective in preventing T-cell proliferation and activation by affecting intracellular Ca2+ homeostasis. Here, we present the structure-activity relationship, KV1.3 inhibition, and immunosuppressive effects of new thiophene-based KV1.3 inhibitors with nanomolar potency on K+ current in T-lymphocytes and KV1.3 inhibition on Ltk− cells. The new KV1.3 inhibitor trans-18 inhibited KV1.3 -mediated current in phytohemagglutinin (PHA)-activated T-lymphocytes with an IC50 value of 26.1 nM and in mammalian Ltk− cells with an IC50 value of 230 nM. The KV1.3 inhibitor trans-18 also had nanomolar potency against KV1.3 in Xenopus laevis oocytes (IC50 = 136 nM). The novel thiophene-based KV1.3 inhibitors impaired intracellular Ca2+ signaling as well as T-cell activation, proliferation, and colony formation.

Keywords

inhibitorji;ionski kanal KV1.3;T-limfocitni imunosupresiv;ion channel;KV1.3 inhibitor;T-lymphocyte;immunosuppressive;

Data

Language: English
Year of publishing:
Typology: 1.01 - Original Scientific Article
Organization: UL FFA - Faculty of Pharmacy
UDC: 577.352:615.37
COBISS: 156924419 Link will open in a new window
ISSN: 0223-5234
Views: 136
Downloads: 32
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Other data

Secondary language: Slovenian
Secondary keywords: Ionski kanalčki;Imunosupresivna biološka zdravila;
Type (COBISS): Article
Pages: 17 str.
Issue: ǂVol. ǂ259, art. 115561
Chronology: 2023
DOI: 10.1016/j.ejmech.2023.115561
ID: 20900289