title: A FRET-Based Assay for the Identification and Characterization of Cereblon Ligands.
abstract: Cereblon serves as an ubiquitin ligase substrate receptor that can be tuned toward different target proteins by various cereblon-binding agents. This offers one of the most promising avenues for targeted protein degradation in cancer therapy, but cereblon binding can also mediate teratogenic effects. We present an effective assay that is suited for high-throughput screening of compound libraries for off-target cereblon interactions but also can guide lead optimization and rational design of novel cereblon effector molecules.
authors.affiliation: Department of Protein Evolution, Max Planck Institute for Developmental Biology , Spemannstrasse 35, 72076 Tübingen, Germany.
authors.forename: Iuliia
authors.initials: I
authors.lastname: Boichenko
authors.affiliation: Department of Protein Evolution, Max Planck Institute for Developmental Biology , Spemannstrasse 35, 72076 Tübingen, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Deiss
authors.affiliation: Department of Protein Evolution, Max Planck Institute for Developmental Biology , Spemannstrasse 35, 72076 Tübingen, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bär
authors.affiliation: Department of Protein Evolution, Max Planck Institute for Developmental Biology , Spemannstrasse 35, 72076 Tübingen, Germany.
authors.forename: Marcus D
authors.initials: MD
authors.lastname: Hartmann
authors.affiliation: Department of Protein Evolution, Max Planck Institute for Developmental Biology , Spemannstrasse 35, 72076 Tübingen, Germany.
authors.forename: Birte
authors.initials: B
authors.lastname: Hernandez Alvarez
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry; D015195:Drug Design; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods*; D057166:High-Throughput Screening Assays; D006801:Humans; D008024:Ligands; D042201:Magnetospirillum / Q000737:chemistry; D008958:Models, Molecular; D010447:Peptide Hydrolases / Q000737:chemistry*; D011485:Protein Binding; D054852:Small Molecule Libraries; D013723:Teratogens / Q000633:toxicity; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C502543:CRBN protein, human; D029742:Caenorhabditis elegans Proteins; D008024:Ligands; D054852:Small Molecule Libraries; D013723:Teratogens; D044767:Ubiquitin-Protein Ligases; D010447:Peptide Hydrolases