Abstract Molecular glue degraders (MGDs) and proteolysis-targeting chimeras (PROTACs) are two prominent approaches in targeted protein degradation, both leveraging the ubiquitin-proteasome system to induce selective protein degradation. While PROTACs rely on heterobifunctional motifs, MGDs possess more compact, mono-affinitive molecular structures, offering distinct advantages in drug-like properties. Over the past decade, significant progress has been made in development of MGDs, with over 20 MGDs advancing through clinical trials. Despite these advancements, the field remains in its early stages due to the novel mode of action and complex design principles. To facilitate rational design of MGDs, we present MolGlueDB, an open-access, web-based database consolidating information from 241 publications (January 2001–May 2025). MolGlueDB contains 1840 entries, including 1629 distinct MGDs, 28 recruiting proteins, and 94 targets, with comprehensive data on chemical structures, binding affinities, degradation capacities, biological activities, and physicochemical properties. The platform supports both text-based and structure-based searches, enabling users to refine results based on specific molecular attributes. MolGlueDB is freely accessible at https://www.molgluedb.com, providing a valuable resource for advancing research of MGDs and accelerating drug discovery in the field of targeted protein degradation.
Wang et al. (Thu,) studied this question.
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