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PXD040668-1

PXD040668 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleITK Degradation to Block T-cell Receptor Signaling and Overcome Therapeutic Resistance in T-Cell Lymphomas
DescriptionIL-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.
HostingRepositoryPRIDE
AnnounceDate2023-05-29
AnnouncementXMLSubmission_2023-05-29_15:11:01.661.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEricFischer
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-03-07 19:02:23ID requested
12023-05-29 15:11:02announced
22023-11-14 09:00:36announced2023-11-14: Updated project metadata.
Publication List
Keyword List
submitter keyword: lymphoma, cereblon, kinase, PROTAC, ubiquitin,degrader, ITK
Contact List
EricFischer
contact affiliationDepartment 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 emaileric_fischer@dfci.harvard.edu
lab head
EricFischer
contact affiliationDana-Farber Cancer Institute
contact emaileric_fischer@dfci.harvard.edu
dataset submitter
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Dataset FTP location
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