PXD035721-1

PXD035721 is an original dataset announced via ProteomeXchange.

Title	Selective androgen receptor degrader (SARD) to overcome antiandrogen resistance in castration-resistant prostate cancer
Description	Clinical resistance such as androgen receptor (AR) mutation, AR overexpression, and AR splice variants (ARVs) restrict the second-generation antiandrogens benefit in patients with castration-resistant prostate cancer (CRPC). Several strategies have been implemented to develop novel antiandrogens to circumvent the occurring resistance. In this study, based on rational drug design, we discovered and identified a bifunctional small molecule Z15 as a potent AR antagonist and AR selective degrader. Z15 could directly bind to the AR ligand-binding domain (LBD) and inhibited DHT-induced AR nuclear translocation. Furthermore, Z15 promoted AR degradation through the proteasome pathway. As a result, our in vitro and in vivo studies showed Z15 efficiently suppressed AR and AR mutant transcription activity, downregulated mRNA and protein levels of AR target genes, as well as overcame AR LBD mutations, AR amplification, and ARVs-induced resistance in CRPC. In conclusion, our data illustrate the synergistic importance of AR antagonism and degradation in advanced prostate cancer treatment.
HostingRepository	PRIDE
AnnounceDate	2023-02-02
AnnouncementXML	Submission_2023-02-02_05:20:04.087.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MengWu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Bruker Daltonics timsTOF series

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-02 02:09:36	ID requested
⏵ 1	2023-02-02 05:20:04	announced
2	2023-11-14 08:57:28	announced	2023-11-14: Updated project metadata.

submitter keyword: Human prostate cancer cell, 4D-label free proteomic analysis, LNCaP

MengWu
contact affiliation	Beijing Hospital
contact email	wumeng_1915@163.com
lab head
MengWu
contact affiliation	Beijing hospital
contact email	wumeng_1915@163.com
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/2023/02/PXD035721

PRIDE project URI

• PRIDE
  1. PXD035721
     1. Label: PRIDE project
     2. Name: Selective androgen receptor degrader (SARD) to overcome antiandrogen resistance in castration-resistant prostate cancer