PXD071969

PXD071969 is an original dataset announced via ProteomeXchange.

Title	ccRCC cells treated with DMSO or UNC8209
Description	Clear cell renal cell carcinoma (ccRCC), the most common kidney cancer subtype, often features inactivation of the VHL tumor suppressor, creating therapeutic vulnerabilities. Although HIF2α inhibitors have shown promise, many VHL-deficient tumors remain resistant. TANK-binding kinase 1 (TBK1) has been identified as a synthetic lethal target in this context. Here, we describe the development of UNC8209, an optimized cereblon-based recruiting Proteolysis-targeting chimeras (PROTACs) that selectively and potently degrades TBK1. Compared to earlier compounds, UNC8209 exhibits enhanced degradation efficiency, improved selectivity over off-target kinases such as IKKε, and robust anti-proliferative activity in VHL-deficient RCC models. Sensitivity to UNC8209 correlates with TBK1 activity in general across cell lines. We also generated a negative control compound that confirms target-specific effects. In addition, UNC8209 effectively suppresses tumor growth in vivo with minimal toxicity, supporting its therapeutic potential as a next-generation TBK1-targeting strategy for VHL-deficient cancers.
HostingRepository	PRIDE
AnnounceDate	2026-03-10
AnnouncementXML	Submission_2026-03-10_05:10:27.770.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lianxin Hu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-13 23:39:23	ID requested
⏵ 1	2026-03-10 05:10:28	announced

Dataset with its publication pending

submitter keyword: LC-MSMS,PROTAC, TBK1, ccRCC

Qing Zhang
contact affiliation	Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
contact email	Qing.Zhang@utsouthwestern.edu
lab head
Lianxin Hu
contact affiliation	Zhejiang University
contact email	lianxin.hu@zju.edu.cn
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/2026/03/PXD071969

PRIDE project URI

• PRIDE
  1. PXD071969
     1. Label: PRIDE project
     2. Name: ccRCC cells treated with DMSO or UNC8209