{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nie X"],"funding":["University of Wisconsin Carbone Cancer Center","NCI NIH HHS","National Institutes of Health","NIH HHS","NIGMS NIH HHS"],"pagination":["e202300685"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10922875"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(4)"],"pubmed_abstract":["Thalidomide, pomalidomide and lenalidomide, collectively referred to as immunomodulatory imide drugs (IMiDs), are frequently employed in proteolysis-targeting chimeras (PROTACs) as cereblon (CRBN) E3 ligase-recruiting ligands. However, their molecular glue properties that co-opt the CRL4<sup>CRBN</sup> to degrade its non-natural substrates may lead to undesired off-target effects for the IMiD-based PROTAC degraders. Herein, we reported a small library of potent and cell-permeable CRBN ligands, which exert high selectivity over the well-known CRBN neo-substrates of IMiDs by structure-based design. They were further utilized to construct bromodomain-containing protein 4 (BRD4) degraders, which successfully depleted BRD4 in the tested cells. Overall, we reported a series of functionalized CRB"],"journal":["Chembiochem : a European journal of chemical biology"],"pubmed_title":["Development of Phenyl-substituted Isoindolinone- and Benzimidazole-type Cereblon Ligands for Targeted Protein Degradation."],"pmcid":["PMC10922875"],"funding_grant_id":["R35GM148266","NIH P30 CA014520","R01 GM137090","R01 GM137090","P30 CA014520","R35 GM148266","T32 GM008505"],"pubmed_authors":["Wang B","Guan H","Xing Y","Sundaresan R","Zhao Y","Tang H","Liao J","Guo L","Zhang Z","Xie H","Tang W","Nie X","Almodovar-Rivera CM"],"additional_accession":[]},"is_claimable":false,"name":"Development of Phenyl-substituted Isoindolinone- and Benzimidazole-type Cereblon Ligands for Targeted Protein Degradation.","description":"Thalidomide, pomalidomide and lenalidomide, collectively referred to as immunomodulatory imide drugs (IMiDs), are frequently employed in proteolysis-targeting chimeras (PROTACs) as cereblon (CRBN) E3 ligase-recruiting ligands. However, their molecular glue properties that co-opt the CRL4<sup>CRBN</sup> to degrade its non-natural substrates may lead to undesired off-target effects for the IMiD-based PROTAC degraders. Herein, we reported a small library of potent and cell-permeable CRBN ligands, which exert high selectivity over the well-known CRBN neo-substrates of IMiDs by structure-based design. They were further utilized to construct bromodomain-containing protein 4 (BRD4) degraders, which successfully depleted BRD4 in the tested cells. Overall, we reported a series of functionalized CRB","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-06-01T12:59:32.544Z","creation":"2025-04-04T01:11:53.927Z"},"accession":"S-EPMC10922875","cross_references":{"pubmed":["38116854"],"doi":["10.1002/cbic.202300685"]}}