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PXD073938
PXD073938 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Quantitative Global Proteomics of Formalin-Fixed Paraffin-Embedded Tumors Identifies Dimethylated G3BP1 at Arginine 460 as a Robust Pharmacodynamic Biomarker of MTAP-Selective PRMT5 Inhibition |
| Description | Inhibition of protein arginine methyltransferase 5 (PRMT5) is synthetic lethal with MTAP-deficient cancers. PRMT5's enzymatic activity can be assessed by measuring symmetric dimethylarginine (SDMA) modification levels of protein substrates. However, conventional assays that attempt to measure total SDMA levels lack the specificity to measure individual PRMT5 substrates, and thus potentially reduce selectivity and sensitivity. This study aims to identify and characterize specific DMA peptides that can serve as clinical pharmacodynamic (PD) biomarkers for PRMT5 inhibition in formalin-fixed paraffin-embedded (FFPE) solid tumors, leveraging data independent acquisition-mass spectrometry (DIA-MS)-based global proteomics without additional DMA enrichment. We evaluated 145 DMA peptides in xenograft models treated by a novel MTAP-selective PRMT5 inhibitor, AZD3470. Arginine dimethylation of G3BP1 at residue R460 (G3BP1(R460)) was identified as the primary PD biomarker for PRMT5 inhibition due to its high abundance and significant post-treatment reduction that correlated with dose. The global proteomics assay with limit of detection/quantification characterized the quantitative performance and allowed for confident detection of G3BP1(R460). Using this quantitative assay, more than 90% reduction in G3BP1(R460) modification at 100 mg/kg was reproducibly detected in MTAP-null xenograft models. Our findings suggested that the DIA-MS proteomics assay can provide high specificity and sensitivity in the detection of PRMT5 inhibition. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-05-06 |
| AnnouncementXML | Submission_2026-05-06_07:41:53.831.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Anqi Tu |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | dimethylated L-arginine |
| Instrument | timsTOF Pro 2 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2026-02-02 12:21:40 | ID requested | |
| ⏵ 1 | 2026-05-06 07:41:55 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: arginine dimethylation, PRMT5 inhibition, DIA, DatasetType:Proteomics |
Contact List
| Andrew Chambers | |
|---|---|
| contact affiliation | AstraZeneca |
| contact email | andrew.chambers@astrazeneca.com |
| lab head | |
| Anqi Tu | |
| contact affiliation | AstraZeneca |
| contact email | anqi.tu@astrazeneca.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/v12/MSV000100693/ |
