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

Povzetek

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.

Ključne besede

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

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL FFA - Fakulteta za farmacijo
UDK: 577.352:615.37
COBISS: 156924419 Povezava se bo odprla v novem oknu
ISSN: 0223-5234
Št. ogledov: 136
Št. prenosov: 32
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: Ionski kanalčki;Imunosupresivna biološka zdravila;
Vrsta dela (COBISS): Članek v reviji
Strani: 17 str.
Zvezek: ǂVol. ǂ259, art. 115561
Čas izdaje: 2023
DOI: 10.1016/j.ejmech.2023.115561
ID: 20900289