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

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

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.

• Language: English
• Keywords: ion channel, K$_V$1.3 inhibitor, T-lymphocyte, immunosuppressive
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 17 str.
• Numbering: Vol. 259, art. 115561
• PID: 20.500.12556/RUL-152203
• UDC: 577.352:615.37
• ISSN on article: 0223-5234
• DOI: 10.1016/j.ejmech.2023.115561
• COBISS.SI-ID: 156924419
• Publication date in RUL: 10.11.2023

Record is a part of a journal

• Title: European journal of medicinal chemistry
• Shortened title: Eur. j. med. chem.
• Publisher: Elsevier
• ISSN: 0223-5234
• COBISS.SI-ID: 25429760

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: inhibitorji, ionski kanal K$_V$1.3, T-limfocitni imunosupresiv, ionski kanalčki, imunosupresivna biološka zdravila