Unlocking SLC6A15 (B ⁰ AT2): A Dual-Platform Approach To Accelerate Drug Discovery for Neuropsychiatric Disorders

AT2), a sodium-dependent neutral amino acid transporter predominantly expressed in the central nervous system, has emerged as a potential therapeutic target in neuropsychiatric disorders. SLC6A15 is a transmembrane protein that facilitates the symport of neutral and branched-chain amino acids, particularly proline, leucine, isoleucine, valine, and methionine, with sodium ions. While knockout studies have revealed its involvement in amino acid transport, food intake regulation, and emotional behavior through glutamatergic signaling modulation, only a few inhibitors, including loratadine and tiagabine, have been identified to date. To advance drug discovery efforts targeting SLC6A15, we developed a novel dual-platform screening approach combining Acoustic Droplet Ejection-Mass Spectrometry (ADE-MS) with Solid Supported Membrane (SSM) electrophysiology. This integrated strategy offers enhanced throughput, sensitivity, and physiological relevance compared to traditional screening methods, potentially accelerating the identification of SLC6A15 modulators for therapeutic applications.