CRBN-based PROTAC Development
CRBN, encoding a 442-amino-acid protein, is identified as a gene responsible for autosomal recessive non-syndromic intellectual disability. Cereblon protac (CRBN) is a ubiquitously expressed protein that is part of the cullin-4 E3 ubiquitin ligase complex, CUL4-RBX1-DDB1 (CRL4). CRBN serves as a substrate receptor of the CRL4 that recognizes substrates for ubiquitination and subsequent proteasomal degradation. CRBN binds to small molecules ligands through the glutarimide moiety and recognizes different neosubstrates depending on the structure.
