PXD062492

PXD062492 is an original dataset announced via ProteomeXchange.

Title	Proteome-guided drug development of effective androgen receptor degraders for prostate cancer
Description	Current drug development processes are slow, costly, and high-risk, posing challenges for advancing safe and effective therapeutics. Here, we present a strategy using high-throughput proteomics to guide the development of androgen receptor (AR)-targeting heterobifunctional degraders (HBDs), a promising but yet-to-be-approved modality for treatment-resistant prostate cancer. We generated a chemically diverse HBD library and leveraged the absence of AR expression in human liver cells to assess off-target effects. In the absence of AR, HBDs induced proteomic responses which reflected degrader chemistries and revealed the off-target toxicity mechanism—respiratory chain complex I inhibition. A proteome-trained machine learning model identified candidates that effectively degraded AR while avoiding off-target interactions. These optimized candidates exhibited reduced hepatotoxicity, enhanced prostate cancer selectivity, and delayed tumor formation in treatment-resistant xenograft models. Our findings pave the way for safer AR degraders and provide a blueprint for proteome-guided drug development.
HostingRepository	PRIDE
AnnounceDate	2026-08-20
AnnouncementXML	Submission_2026-08-20_04:26:36.618.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shaon Basu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-01 20:12:00	ID requested
⏵ 1	2026-08-20 04:26:37	announced

Dataset with its publication pending

submitter keyword: Machine Learning, Drug Screen,Proteomics, Drug Development, Toxicology, PROTAC, Pharmacology

Prof. Dr.
contact affiliation	Charité – Universitätsmedizin Berlin
contact email	markus.ralser@charite.de
lab head
Shaon Basu
contact affiliation	Charité – Universitätsmedizin Berlin
contact email	shaon.basu@charite.de
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/2026/07/PXD062492

PRIDE project URI

• PRIDE
  1. PXD062492
     1. Label: PRIDE project
     2. Name: Proteome-guided drug development of effective androgen receptor degraders for prostate cancer