PXD057859

PXD057859 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-13 12:14:27	ID requested
⏵ 1	2025-05-07 05:02:01	announced

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;

submitter keyword: ALL cell line LC-MSMS

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

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

• PRIDE
  1. PXD057859
     1. Label: PRIDE project
     2. Name: KT-253, A Novel MDM2 Degrader and p53 Stabilizer, Has Superior Potency and Efficacy Than MDM2 Small Molecule Inhibitors