Molecular Glues

Molecular glues are a class of low molecular weight compounds that can enhance the interaction between two proteins. In the process of promoting the interaction between proteins and E3 ligases, triggering the ubiquitination and subsequent degradation of target proteins, these compounds are called molecular glue degraders (MGDs). Currently, there are two main categories of mature molecular glues: one is immunomodulatory drugs (IMiDs), which can bind to E3 CRBN, recruit transcription factors containing zinc finger (ZF) domain factors for ubiquitination and degradation by proteasomes, while IMiDs themselves have no measurable binding affinity for degrading transcription factors. The three major molecular glue drugs currently on the market, thalidomide, lenalidomide and pomalidomide, all belong to this category and are used to treat multiple myeloma, myelodysplastic syndrome, etc. The other category is aromatic sulfonamides, such as indisulam and tasisulam, which can bind to E3 DCAF15 and recruit splicing factor RNA binding motif protein 39 (RBM39) for ubiquitination and degradation.