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PXD035721-1

PXD035721 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSelective androgen receptor degrader (SARD) to overcome antiandrogen resistance in castration-resistant prostate cancer
DescriptionClinical 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.
HostingRepositoryPRIDE
AnnounceDate2023-02-02
AnnouncementXMLSubmission_2023-02-02_05:20:04.087.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMengWu
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentBruker Daltonics timsTOF series
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-08-02 02:09:36ID requested
12023-02-02 05:20:04announced
22023-11-14 08:57:28announced2023-11-14: Updated project metadata.
Publication List
Keyword List
submitter keyword: Human prostate cancer cell, 4D-label free proteomic analysis, LNCaP
Contact List
MengWu
contact affiliationBeijing Hospital
contact emailwumeng_1915@163.com
lab head
MengWu
contact affiliationBeijing hospital
contact emailwumeng_1915@163.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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