PXD057859 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | KT-253, A Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy Than MDM2 Small Molecule Inhibitors |
Description | KT-253 is a potent and selective heterobifunctional MDM2 degrader with superior activity to MDM2/p53 small molecule inhibitors. RS4;11 cells treated with KT-253 indicated no off-target protein degradation. All significantly upregulated proteins are p53 and its target genes. KT-253 overcomes p53/MDM2 feedback loop. Targeted proteomics analysis of MDM2 levels in RS4;11 cells shows that KT-253 (150 nM KT-253 for 15 minutes) can achieve greater than 90% degradation of MDM2 within 1 hour posttreatment, whereas MDM2 levels continued to increase 1 hour after treatment with DS-3032 A single dose of KT-253 drives sustained tumor regression in ALL xenografts. Targeted proteomic analysis of tumors demonstrates robust degradation of MDM2 1-hour post dosing with KT-253. This is associated with activation of the p53 pathway as evidenced by a corresponding upregulation of proteomics biomarkers p53, p21, and PHLDA3. |
HostingRepository | PRIDE |
AnnounceDate | 2025-05-07 |
AnnouncementXML | Submission_2025-05-07_05:02:00.377.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Kymera Proteomics |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue |
Instrument | Q Exactive HF; LTQ Orbitrap Elite |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-11-13 12:14:27 | ID requested | |
⏵ 1 | 2025-05-07 05:02:01 | announced | |
Publication List
Chutake YK, Mayo MF, Dumont N, Filiatrault J, Breitkopf SB, Cho P, Chen D, Dixit VS, Proctor WR, Kuhn EW, Bollinger Martinez S, McDonald AA, Qi J, Hu KN, Karnik R, Growney JD, Sharma K, Schalm SS, Gollerkeri AM, Mainolfi N, Williams JA, Weiss MM, KT-253, a Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy than MDM2 Small-Molecule Inhibitors. Mol Cancer Ther, 24(4):497-510(2025) [pubmed] |
10.1158/1535-7163.mct-24-0306; |
Keyword List
submitter keyword: ALL cell line LC-MSMS |
Contact List
Susanne Breitkopf |
contact affiliation | Proteomics, Kymera, Inc. USA |
contact email | sbreitkopf@kymeratx.com |
lab head | |
Kymera Proteomics |
contact affiliation | Kymera Therapeutics |
contact email | proteomics_user@kymeratx.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD057859 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD057859
- Label: PRIDE project
- Name: KT-253, A Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy Than MDM2 Small Molecule Inhibitors