The successful discovery of these lead Thalidomide analogs, also referred to as Cereblon E3 Ligase Modulation Drugs (CELMoDs), serves as a paradigm for using SBDD in the development of lead molecular glue degraders. Next, we will review the SBDD of CELMoDs from thalidomide, pomalidomide and lenalidomide as an example to illustrate steps to develop molecular glue degraders; including: scaffold definition, identification of optimal of scaffold analogs and validation of lead compounds.