Table 2. Pathway of Molecular Glue Degrader Discovery and Structure-Guided Drug Design.

initial discovery	scaffold definition	optimization	validation
serendipitous30	crystallography63,64	protein–protein interaction assay of scaffold analogues68	binding assays69
high-throughput screens (HTS)52,60,61	molecular docking65,66	E3 ligase-dependent activity assay of scaffold analogues66,67	biochemical methods validating target degradation46,67
data mining62	structure–activity relationship (SAR) studies66−68		cell-based activity assays68
			molecular docking analysis67
			crystallography69,70