Molecular glue degraders (MGDs) induce the proximity of target proteins to E3 ubiquitin ligases, leading to target protein ubiquitination and subsequent degradation by the proteasome. Unlike conventional inhibitors that target enzymatic activity, these molecules enable the degradation of proteins previously deemed "undruggable," thereby rendering them "druggable". With a first-in-class VAV1-directed MGDs (MRT6160) enters in clinical phase I, VAV1 degraders showed the remarkable potential in Immunology and inflammatory diseases such as rheumatoid arthritis and colitis. Current advancements highlight its ability to reduce proinflammatory cytokine production, inhibit pathogenic T cell polarization, and mitigate autoimmune responses.
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