PXD061539

PXD061539 is an original dataset announced via ProteomeXchange.

Title	Development of PROTACs for in vivo AURKA degradation in neuroblastoma
Description	Aurora Kinase A (AURKA) is a well-established oncogenic factor and potent drug target in neuroblastoma given its crucial role during mitosis, MYCN-stabilization, DNA damage repair and replication fork stability. We previously reported a highly potent, selective and fast-acting AURKA degrader, SK2188, which inhibited tumor cell growth more potently than its parent inhibitor, indicating potential therapeutic benefits of AURKA degradation compared to inhibition. Despite these promising results, SK2188 showed low exposure and rapid clearance in mice following administration, thus hampering further in vivo evaluation and indicating the need for further chemical optimization. In this study, we describe our structure/activity optimization efforts involving linker rigidification and the integration of alternative cereblon- and AURKA-recruiting ligands. These efforts culminated in the rational design of PROTACs SK4454 and SK5527. This LC-MSMS analysis was performed to analyze the short-term (3h) and long-term (24h) effects of SK5527 on the proteome. Our data confirms SK5527 to have a selective AURKA degradation profile.
HostingRepository	PRIDE
AnnounceDate	2025-11-20
AnnouncementXML	Submission_2025-11-20_06:15:25.891.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Teresa Mendes Maia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-06 11:03:19	ID requested
⏵ 1	2025-11-20 06:15:26	announced

10.1021/ACS.JMEDCHEM.5C01271;

submitter keyword: Aurora Kinase A,LC-MSMS, SK5527, PROTACs

Kaat Durinck
contact affiliation	Pediatric Precision Oncology Lab (PPOL), Department of Biomolecular Medicine, Faculty of Medicine & Health Sciences, Ghent University, Corneel Heymanslaan 10, 9000 Ghent, Belgium
contact email	Kaat.Durinck@UGent.be
lab head
Teresa Mendes Maia
contact affiliation	VIB Proteomics Core
contact email	teresa.maia@vib-ugent.be
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/2025/11/PXD061539

PRIDE project URI

• PRIDE
  1. PXD061539
     1. Label: PRIDE project
     2. Name: Development of PROTACs for in vivo AURKA degradation in neuroblastoma