细胞内
爪蟾
化学
IC50型
效力
噻吩
细胞生长
钾通道
结构-活动关系
细胞生物学
药理学
生物化学
生物物理学
体外
生物
有机化学
基因
作者
Špela Gubič,Alberto Montalbano,Cesare Sala,Andrea Becchetti,Louise Antonia Hendrickx,Kenny M. Van Theemsche,Ernesto Lopes Pinheiro-Júnior,Ginevra Chioccioli Altadonna,Steve Peigneur,Janez Ilaš,Alain J. Labro,Luis A. Pardo,Jan Tytgat,Tihomir Tomašič,Annarosa Arcangeli,Lucíja Peterlin Mašič
标识
DOI:10.1016/j.ejmech.2023.115561
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI