PXD063662

PXD063662 is an original dataset announced via ProteomeXchange.

Title	Identification of drug repurposing candidates for the treatment of polycystic kidney disease - Birinapant
Description	Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of end-stage renal disease with limited treatment options. Drug repurposing offers a promising strategy to find effective treatments. We identified birinapant, bardoxolone methyl and salicylic acid as repurposing candidates for ADPKD and applied thermal proteome profiling to identify disease-relevant targets. Our results uncovered shared effects between the three drugs, including a thermal shift in ADP/ATP translocases (SLC25A4/5/6) caused by reduced ATP production. As expected, salicylic acid displayed a polypharmacological profile but also engaged enzymes along the N-linked glycosylation pathway and inhibited PTK2, an activator of the proliferative PI3K/Akt/mTOR pathway. Orthogonal assays and computational modelling confirmed these findings and located the binding site (499-504) of salicylic acid within PTK2’s ATP-binding pocket. Engagement of several targets was achieved at clinically relevant concentrations. We have identified novel targets of three repurposing candidates that contribute to the cyst growth reducing effects in preclinical ADPKD models and identify salicylic acid, the metabolite of aspirin, as the repurposing candidate with the most promising mechanisms of action. This dataset contains files from thermal proteome profiling after birinapant exposure.
HostingRepository	PRIDE
AnnounceDate	2026-05-18
AnnouncementXML	Submission_2026-05-18_13:58:24.043.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alina Meyer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-06 08:14:42	ID requested
⏵ 1	2026-05-18 13:58:25	announced

10.1111/BPH.70493;

submitter keyword: None

Per Artursson
contact affiliation	Professor at Department of Pharmacy, Drug Delivery, Uppsala University
contact email	per.artursson@uu.se
lab head
Alina Meyer
contact affiliation	Department of Pharmacy, Uppsala University
contact email	alina.meyer@farmaci.uu.se
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/2026/05/PXD063662

PRIDE project URI

• PRIDE
  1. PXD063662
     1. Label: PRIDE project
     2. Name: Identification of drug repurposing candidates for the treatment of polycystic kidney disease - Birinapant