SH2scan: Mapping SH2 domain-ligand binding selectivity for inhibitors and degraders

Drug discovery targeting SH2 domains (key protein-protein interaction modules) has been hampered by a lack of assay systems evaluating SH2 domain-synthetic ligand binding selectivity to reduce potential off-target effects. Here, we developed SH2 scan , a high-throughput competition binding assay platform used to quantify ligand-SH2 domain interactions, covering >80% of the target class. This platform can be used to design more selective compounds targeting SH2 domains.