English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/165285
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Identification of a Drug Targeting an Intrinsically Disordered Protein Involved in Pancreatic Adenocarcinoma

AuthorsNeira, J.L.; Bintz, J.; Arruebo, M.; Rizzuti, B.; Bonacci, T.; Vega, Sonia; Lanas, A.; Velazquez-Campoy, Adrian; Iovanna, Juan Lucio; Abian, Olga
Issue Date2017
PublisherNature Publishing Group
CitationScientific Reports 7 (2017)
AbstractIntrinsically disordered proteins (IDPs) are prevalent in eukaryotes, performing signaling and regulatory functions. Often associated with human diseases, they constitute drug-development targets. NUPR1 is a multifunctional IDP, over-expressed and involved in pancreatic ductal adenocarcinoma (PDAC) development. By screening 1120 FDA-approved compounds, fifteen candidates were selected, and their interactions with NUPR1 were characterized by experimental and simulation techniques. The protein remained disordered upon binding to all fifteen candidates. These compounds were tested in PDAC-derived cell-based assays, and all induced cell-growth arrest and senescence, reduced cell migration, and decreased chemoresistance, mimicking NUPR1-deficiency. The most effective compound completely arrested tumor development in vivo on xenografted PDAC-derived cells in mice. Besides reporting the discovery of a compound targeting an intact IDP and specifically active against PDAC, our study proves the possibility to target the 'fuzzy' interface of a protein that remains disordered upon binding to its natural biological partners or to selected drugs.
Identifiersdoi: 10.1038/srep39732
issn: 2045-2322
Appears in Collections:(IQFR) Artículos
Files in This Item:
File Description SizeFormat 
srep39732.pdf1,33 MBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.