PXD059271-1

PXD059271 is an original dataset announced via ProteomeXchange.

Title	Development of A Image-based High-content Screening Assay Based on Clickable Probes for Identification of XPB Inhibitors
Description	High-content screening (HCS) has become a powerful tool in drug discovery; however, their reliance on indirect readouts and surrogate markers limits their ability to directly assess drug-protein interactions at endogenous levels, particularly in subcellular contexts. Here, we report the development of a confocal image-based HCS platform that addresses these limitations by combining with bio-orthogonal labelling. We synthesized a clickable probe TL-alkyne that rapidly and specifically labels xeroderma pigmentosum type B (XPB), a critical protein in the nucleotide excision repair (NER). The colorimetric HCS assay enabled direct and precise measurement of drug occupancy rates in XPB specifically within the nucleus of live cells. Out of 1,953 FDA-approved drugs, pelitinib was identified as a novel ligand to bind XPB. It formed a covalent bond with Cys342 of XPB, suppressed XPB's ATPase activity, impaired nucleotide excision repair, and synergistically enhanced chemotherapy. This study demonstrates the transformative potential of integrating click chemistry with advanced HCS technologies, offering a robust framework for high-throughput drug discovery targeting challenging protein systems
HostingRepository	PRIDE
AnnounceDate	2025-09-08
AnnouncementXML	Submission_2025-09-07_16:22:41.881.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yang Yang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-26 23:19:20	ID requested
⏵ 1	2025-09-07 16:22:42	announced

10.1002/anie.202505585;

Li S, Zhang HR, Yang Y, Ko BC, Shang J, Guo H, Yang D, Wong M, Chan RW, Kung KK, Zhao Q, Imaging-Based High-Content Screening with Clickable Probes Identifies XPB Inhibitors. Angew Chem Int Ed Engl, 64(36):e202505585(2025) [pubmed]

submitter keyword: High-content Screening, Click Chemistry,XPB

Qian Zhao
contact affiliation	The Hong Kong Polytechnic University
contact email	shuqi.li@connect.polyu.hk
lab head
Yang Yang
contact affiliation	The Hong Kong Polytechnic University
contact email	yangss.yang@connect.polyu.hk
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/2025/09/PXD059271

PRIDE project URI

• PRIDE
  1. PXD059271
     1. Label: PRIDE project
     2. Name: Development of A Image-based High-content Screening Assay Based on Clickable Probes for Identification of XPB Inhibitors