{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Campos MA"],"funding":["NCI NIH HHS","NIGMS NIH HHS"],"pagination":["479-488"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11973735"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["20(2)"],"pubmed_abstract":["Conventional small-molecule drugs primarily operate by inhibiting protein function, but this approach is limited when proteins lack well-defined ligand-binding pockets. Targeted protein degradation (TPD) offers an alternative approach by harnessing cellular degradation pathways to eliminate specific proteins. Recent studies have expanded the potential of TPD by identifying additional E3 ligases, with DCAF16 emerging as a promising candidate for facilitating protein degradation through both proteolysis-targeting chimera (PROTAC) and molecular glue mechanisms. In this study, we revisited a previously reported compound and discovered that it covalently binds to DCAF16. We further optimized it into a FKBP12-targeting PROTAC, MC-25B. This PROTAC engages DCAF16 at cysteines C177-179, leading to "],"journal":["ACS chemical biology"],"pubmed_title":["Discovery of DCAF16 Binders for Targeted Protein Degradation."],"pmcid":["PMC11973735"],"funding_grant_id":["R00 CA248715","T32 GM149439"],"pubmed_authors":["Scheidt KA","Zhang X","Riha IA","Mozes C","Zhang C","Campos MA"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of DCAF16 Binders for Targeted Protein Degradation.","description":"Conventional small-molecule drugs primarily operate by inhibiting protein function, but this approach is limited when proteins lack well-defined ligand-binding pockets. Targeted protein degradation (TPD) offers an alternative approach by harnessing cellular degradation pathways to eliminate specific proteins. Recent studies have expanded the potential of TPD by identifying additional E3 ligases, with DCAF16 emerging as a promising candidate for facilitating protein degradation through both proteolysis-targeting chimera (PROTAC) and molecular glue mechanisms. In this study, we revisited a previously reported compound and discovered that it covalently binds to DCAF16. We further optimized it into a FKBP12-targeting PROTAC, MC-25B. This PROTAC engages DCAF16 at cysteines C177-179, leading to ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Feb","modification":"2026-07-16T12:23:01.994Z","creation":"2026-07-09T10:55:31.425Z"},"accession":"S-EPMC11973735","cross_references":{"pubmed":["39882752"],"doi":["10.1021/acschembio.4c00799"]}}