PXD040668 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | ITK Degradation to Block T-cell Receptor Signaling and Overcome Therapeutic Resistance in T-Cell Lymphomas |
Description | IL-2-inducible T cell kinase (ITK) is essential for T cell receptor (TCR) signaling and plays an integral role in T-cell proliferation and differentiation. Unlike the ITK homolog BTK, no inhibitors of ITK are currently FDA approved. In addition, recent studies have identified mutations within BTK that confer resistance to both covalent and non-covalent inhibitors. Here, as an alternative strategy, we report the development of BSJ-05-037, a potent and selective heterobifunctional degrader of ITK. BSJ-05-037 displayed enhanced anti-proliferative effects relative to its parent catalytic inhibitor, blocked the activation of NF-kB/GATA-3 signaling and increased the sensitivity of T cell lymphoma cells to cytotoxic chemotherapy both in vitro and in vivo. In summary, targeted degradation of ITK is a novel approach to modulate TCR signal strength that could have broad application for the investigation and treatment of T cell-mediated diseases. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_09:00:35.731.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Eric Fischer |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-03-07 19:02:23 | ID requested | |
1 | 2023-05-29 15:11:02 | announced | |
⏵ 2 | 2023-11-14 09:00:36 | announced | 2023-11-14: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: lymphoma, cereblon, kinase, PROTAC, ubiquitin,degrader, ITK |
Contact List
Eric Fischer |
contact affiliation | Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA |
contact email | eric_fischer@dfci.harvard.edu |
lab head | |
Eric Fischer |
contact affiliation | Dana-Farber Cancer Institute |
contact email | eric_fischer@dfci.harvard.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD040668
- Label: PRIDE project
- Name: ITK Degradation to Block T-cell Receptor Signaling and Overcome Therapeutic Resistance in T-Cell Lymphomas