Case Study: Kir4.2 Ion Channel

The Kir4.2 ion channel is a promising target in neurological and metabolic diseases, but its inherent instability makes it notoriously difficult to purify or probe with traditional assay systems. With few known ligands and poor compatibility with conventional screens, hit discovery has remained a bottleneck.

Using CARMS, we screened a natural product library directly against semi-purified Kir4.2. Unlike conventional methods, CARMS does not require the protein to be detectable under standard MS conditions, allowing us to directly identify true binders in a streamlined workflow. We identified a novel binder, ginsenoside Rg1, and compared its binding affinity to that of the known ligand polymyxin B.

CARMS enabled the discovery of a novel Kir4.2-binding compound, with no false positives observed in controls. The full screen was completed in under two weeks, demonstrating CARMS as a rapid and reliable approach for hit discovery on challenging targets.