The novel quinoline derivative SKA-346 as a K_Ca3.1 channel selective activator.

ABSTRACT: The calcium-activated K_Ca3.1 channel plays a crucial role in T-cell immune response. Genetic manipulation of T-cells to upregulate the expression of K⁺ channels has been shown to boost T-cell cytotoxicity in cancer. Here, we aimed to identify and characterize an activator that would augment K_Ca3.1 currents without affecting other channels. We synthesized five quinoline derivatives and used electrophysiology to screen them on K_Ca3.1 and a panel of 14 other ion channels. One quinoline derivative, SKA-346, activated K_Ca3.1 with an EC₅₀ of 1.9 μM and showed selectivity against the other channels. In silico analysis using RosettaLigand and GLIDE demonstrated a well-converged pose of SKA-346 in a binding pocket at the inter

SUBMITTER: Wong BHS 

PROVIDER: S-EPMC11615718 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature