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PXD039828

PXD039828 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDevelopment and characterization of selective FAK inhibitors and PROTACs with in vivo activity
DescriptionFocal adhesion kinase (FAK) is an attractive drug target due to its overexpression in cancer. FAK functions as a non-receptor tyrosine kinase and scaffolding protein, coordinating several downstream signaling effectors and cellular processes. While drug discovery efforts have largely focused on targeting FAK kinase activity, FAK inhibitors have failed to show efficacy as single agents in clinical trials. Here, using structure-guided design, we report the development of a selective FAK inhibitor (BSJ-04-175) and degrader (BSJ-04-146) to evaluate the consequences and advantages of abolishing all FAK activity in cancer models. BSJ-04-146 achieves rapid and potent FAK degradation with high proteome-wide specificity in cancer cells and induces remarkably durable degradation in tumor-bearing mice. Compared to kinase inhibition, targeted degradation of FAK exhibits pronounced improved activity on downstream signaling and cancer cell viability and migration. Together, BSJ-04-175 and BSJ-04-146 are valuable chemical tools to dissect the specific consequences of targeting FAK through small molecule inhibition or degradation.
HostingRepositoryPRIDE
AnnounceDate2025-05-06
AnnouncementXMLSubmission_2025-05-06_09:25:58.532.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBehnam Nabet
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-02-03 06:02:19ID requested
12025-05-06 09:25:59announced
Publication List
Koide E, Mohardt ML, Doctor ZM, Yang A, Hao M, Donovan KA, Kuismi CC, Nelson AJ, Abell K, Aguiar M, Che J, Stokes MP, Zhang T, Aguirre AJ, Fischer ES, Gray NS, Jiang B, Nabet B, Development and Characterization of Selective FAK Inhibitors and PROTACs with In Vivo Activity. Chembiochem, 24(19):e202300141(2023) [pubmed]
10.1002/cbic.202300141;
Keyword List
submitter keyword: FAK, inhibitor, PROTAC, degrader
Contact List
Behnam Nabet
contact affiliationFred Hutch Cancer Center, Human Biology Division
contact emailbnabet@fredhutch.org
lab head
Behnam Nabet
contact affiliationFred Hutchinson Cancer Center
contact emailbnabet@fredhutch.org
dataset submitter
Full Dataset Link List
Dataset FTP location
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Repository Record List
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