PXD059111-1
PXD059111 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Unbiased mapping of cereblon neosubstrate landscape by high-throughput proteomics |
| Description | Molecular glue degraders (MGDs) are small molecules that harness the ubiquitin-proteasome system to induce degradation of target proteins, including those lacking conventional druggable pockets. Given the challenges in their rational design, MGD discovery predominantly relies on screening-based approaches, such as cell viability assays. However, one potential limitation of such screening methods is the risk of overlooking non-essential neosubstrates of potential therapeutic value. To address this concern, we present a high-throughput proteome-wide MGD screening platform utilizing label-free, data-independent acquisition mass spectrometry (DIA-MS) for integrated proteomics and ubiquitinomics analysis. Processing a diverse set of 100 CRBN-ligands across two cancer cell lines reveals a broad array of neosubstrates, including 50 novel candidates validated by MS-based ubiquitinomics. These findings considerably expand the current landscape of CRBN-mediated neosubstrates. Comprehensive hit validation and structure-degradation relationship analyses guided by global proteomics, identifies highly selective and potent phenyl glutarimide-based degraders of novel neosubstrates, including KDM4B, G3BP2 and VCL, none of which contain the classical CRBN degron motif. This study demonstrates that comprehensive, high-throughput proteomic screening offers new opportunities in MGD drug discovery. |
| HostingRepository | MassIVE |
| AnnounceDate | 2025-06-12 |
| AnnouncementXML | Submission_2025-06-12_05:16:23.511.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Martin Steger |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | ubiquitination signature dipeptidyl lysine |
| Instrument | timsTOF Pro; timsTOF HT; timsTOF Ultra 2 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-12-20 23:41:51 | ID requested | |
| ⏵ 1 | 2025-06-12 05:16:23 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Molecular glue degrader, cereblon, proteomics screeening, ubiquitinomics, DatasetType:Proteomics |
Contact List
| Zoran Rankovic | |
|---|---|
| contact affiliation | institute of cancer research |
| contact email | zoran.rankovic@icr.ac.uk |
| lab head | |
| Martin Steger | |
| contact affiliation | NEOsphere Biotechnologies GmbH |
| contact email | martin.steger@neospherebiotech.com |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive-ftp.ucsd.edu/v07/MSV000096721/ |
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