PXD050650 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Targeting cancer with small molecule pan-KRAS degraders |
Description | Despite 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 residue1. 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 demand2. Here we show that a single small molecule can be used to simultaneously and potently degrade 13 out of 17 of the most prevalent oncogenic KRAS alleles, including those not yet tractable by inhibitors. Compared with inhibition, degradation of oncogenic KRAS results in more 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 is the proteomics analysis of ACBI3 and compoun 8, its negative control. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-01 |
AnnouncementXML | Submission_2024-10-01_09:12:02.916.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Vesna Vetma |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Ascend |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-03-15 03:56:37 | ID requested | |
⏵ 1 | 2024-10-01 09:12:03 | announced | |
Publication List
Keyword List
submitter keyword: cancer,KRAS, PROTAC |
Contact List
Alessio Ciulli |
contact affiliation | Centre For Targeted Protein Degradation (CeTPD) University of Dundee 1 Lindsay Place, DD1 5JJ Dundee, UK |
contact email | a.ciulli@dundee.ac.uk |
lab head | |
Vesna Vetma |
contact affiliation | University of Dundee |
contact email | v.vetma@dundee.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD050650
- Label: PRIDE project
- Name: Targeting cancer with small molecule pan-KRAS degraders