Affinity selection mass spectrometry (AS-MS) as a tool to accelerate drug discovery efforts

INTRODUCTION: Affinity selection mass spectrometry (AS-MS) is a powerful label-free technique for characterizing macromolecule-ligand interactions that has been used as a hit finding tool with significant success. Recent advances in MS and separation technology have positioned AS-MS to impact more areas of drug discovery. AREAS COVERED: This manuscript provides a brief historical review of AS-MS and the recently developed technologies that have enabled AS-MS. The report also provides examples and references for how AS-MS has been used for high-throughput screening (HTS) to DNA-encoded library (DEL) screening hit confirmation, Direct-to-Biology, and natural product screens. The references for this work were collected from a broad range of sources, including Google Scholar, Scopus, review articles identified via Google Scholar, and the internal AI resource at AbbVie Inc. EXPERT OPINION: AS-MS is a unique biophysical binding assay that does not rely on labels and can specifically detect binders from large pools of potential ligands based on molecular weight. There is still significant room for growth in areas of impact that will be driven by decreases in separation time and a move toward equilibrium conditions during separation. Increased use for driving rapid structure-activity relationships (SAR) has potential to decrease project cycle times in lead identification and optimization.