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PXD057859

PXD057859 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleKT-253, A Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy Than MDM2 Small Molecule Inhibitors
DescriptionKT-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.
HostingRepositoryPRIDE
AnnounceDate2025-05-07
AnnouncementXMLSubmission_2025-05-07_05:02:00.377.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKymera Proteomics
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue
InstrumentQ Exactive HF; LTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-11-13 12:14:27ID requested
12025-05-07 05:02:01announced
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 affiliationProteomics, Kymera, Inc. USA
contact emailsbreitkopf@kymeratx.com
lab head
Kymera Proteomics
contact affiliationKymera Therapeutics
contact emailproteomics_user@kymeratx.com
dataset submitter
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Dataset FTP location
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PRIDE project URI
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