High-throughput screening remains one of the most powerful, unbiased approaches in drug discovery for revealing novel small molecule modulators of biochemical and cellular activities. However, not all therapeutic targets exhibit functional activity and are therefore not amenable to traditional biochemical assays. Affinity selection mass spectrometry (ASMS) has emerged as an attractive screening strategy for challenging protein and oligonucleotide targets, particularly those that do not exhibit functional activity.
The emergence of targeted protein degradation through PROTACs, for example, has motivated the need for rapid screening assays that identify non-covalent binding molecules to initiate development. The general ASMS strategy encompasses incubating the target with a single or pool of small molecules, isolating the target-small molecule complex, and then detecting the binding molecule using mass spectrometry.
This workflow has been applied with some variations using distinct methodologies and MS instrumentation. Understanding the advantages and limitations of these approaches is critical for selecting which technique is suitable for the target and gives the highest likelihood for achieving drug discovery goals.
Register for this webinar to hear a discussion of key aspects to consider for maximizing opportunities to integrate a successful ASMS assay for drug discovery, including the small molecule library, the specific ASMS methodology and converting ASMS hits into promising leads. The webinar will highlight a recently described novel ASMS approach that combines surface chemistry with matrix assisted laser desorption ionization (MALDI) MS and the opportunities it affords for screening virtually any target.