{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Luo M"],"funding":["NIEHS NIH HHS","Mark Foundation For Cancer Research","National Cancer Institute","NCI NIH HHS","Novartis Institutes for BioMedical Research","NIGMS NIH HHS"],"pagination":["559-566.e15"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8052289"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["28(4)"],"pubmed_abstract":["The translation of functionally active natural products into fully synthetic small-molecule mimetics has remained an important process in medicinal chemistry. We recently discovered that the terpene natural product nimbolide can be utilized as a covalent recruiter of the E3 ubiquitin ligase RNF114 for use in targeted protein degradation-a powerful therapeutic modality within modern-day drug discovery. Using activity-based protein profiling-enabled covalent ligand-screening approaches, here we report the discovery of fully synthetic RNF114-based recruiter molecules that can also be exploited for PROTAC applications, and demonstrate their utility in degrading therapeutically relevant targets, such as BRD4 and BCR-ABL, in cells. The identification of simple and easily manipulated drug-like sc"],"journal":["Cell chemical biology"],"pubmed_title":["Chemoproteomics-enabled discovery of covalent RNF114-based degraders that mimic natural product function."],"pmcid":["PMC8052289"],"funding_grant_id":["R01 CA240981","F31 CA239327","R01 GM136945","F99 CA253717","R01 ES028096"],"pubmed_authors":["Tong B","Nomura DK","Schirle M","Luo M","Maimone TJ","Tallarico JA","McKenna JM","Brittain SM","Spradlin JN","Boike L"],"additional_accession":[]},"is_claimable":false,"name":"Chemoproteomics-enabled discovery of covalent RNF114-based degraders that mimic natural product function.","description":"The translation of functionally active natural products into fully synthetic small-molecule mimetics has remained an important process in medicinal chemistry. We recently discovered that the terpene natural product nimbolide can be utilized as a covalent recruiter of the E3 ubiquitin ligase RNF114 for use in targeted protein degradation-a powerful therapeutic modality within modern-day drug discovery. Using activity-based protein profiling-enabled covalent ligand-screening approaches, here we report the discovery of fully synthetic RNF114-based recruiter molecules that can also be exploited for PROTAC applications, and demonstrate their utility in degrading therapeutically relevant targets, such as BRD4 and BCR-ABL, in cells. The identification of simple and easily manipulated drug-like sc","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Apr","modification":"2026-05-02T22:40:44.806Z","creation":"2025-04-04T13:30:32.661Z"},"accession":"S-EPMC8052289","cross_references":{"pubmed":["33513350"],"doi":["10.1016/j.chembiol.2021.01.005"]}}