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PXD045460

PXD045460 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTargeting cancer with small molecule panKRAS degraders
DescriptionDespite the high prevalence of cancers driven by KRAS mutations, to date only the G12C mutation has been clinically proven to be druggable via covalent targeting of the mutated cysteine amino acid residue. However, in many cancer indications other KRAS mutations, such as G12D and -V, are far more prevalent and small molecule concepts that can address a wider variety of oncogenic KRAS alleles are in high clinical demand. Here we show that a single small molecule degrader can be used to simultaneously and potently target multiple KRAS alleles, including those not yet tractable by inhibitors. Degradation of oncogenic KRAS results in profound and sustained pathway modulation across a broad range of KRAS mutant cell lines. As a result, KRAS degraders inhibit growth of the majority of cancer cell lines driven by KRAS mutations while sparing models without genetic KRAS aberrations. Finally, we demonstrate that pharmacological degradation of oncogenic KRAS leads to tumour regression in vivo. Together, these findings unveil a new path towards addressing KRAS driven cancers with small molecule degraders. This experiment corresponds to Figure 2g
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_07:00:14.176.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterVesna Vetma
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-09-18 05:41:24ID requested
12024-10-01 09:22:11announced
22024-10-22 07:00:14announced2024-10-22: Updated project metadata.
Publication List
10.1126/SCIENCE.ADM8684;
Keyword List
submitter keyword: cancer,PROTAC, degradation,KRAS
Contact List
Alessio Ciulli
contact affiliationCentre for targeted protein degradation, University of Dundee
contact emaila.ciulli@dundee.ac.uk
lab head
Vesna Vetma
contact affiliationUniversity of Dundee
contact emailv.vetma@dundee.ac.uk
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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