60404 20190709135526.0 doi 10.1038/srep39732 sideral 97889 ART-2017-97889 eng Neira, J.L. Identification of a Drug Targeting an Intrinsically Disordered Protein Involved in Pancreatic Adenocarcinoma 2017 Access copy available to the general public Unrestricted Intrinsically 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. info:eu-repo/grantAgreement/ES/MINECO/CTQ2015-64445-R info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064-P info:eu-repo/grantAgreement/ES/FIS/PI15-00663 info:eu-repo/grantAgreement/ES/FIS/PI11-02578 info:eu-repo/grantAgreement/ES/FIS/PI10-00186 info:eu-repo/grantAgreement/ES/DGA/B89 info:eu-repo/grantAgreement/ES/DGA/B01 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.122 2017 MULTIDISCIPLINARY SCIENCES 12 / 64 = 0.188 2017 Q1 T1 1.533 2017 Multidisciplinary 2017 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Bintz, J. Arruebo, M. Rizzuti, B. Bonacci, T. (orcid)0000-0002-1232-6310 Vega, S. (orcid)0000-0001-5932-2889 Lanas, A. Universidad de Zaragoza (orcid)0000-0001-5702-4538 Velázquez-Campoy, A. Universidad de Zaragoza Iovanna, J.L. (orcid)0000-0001-5664-1729 Abián, O. Universidad de Zaragoza 1007 610 Universidad de Zaragoza Dpto. Medicina, Psiqu. y Derm. Area Medicina 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 7 (2017), [15 pp.] Sci. rep. Scientific reports 2045-2322 1363982 http://zaguan.unizar.es/record/60404/files/texto_completo.pdf Versión publicada 107763 http://zaguan.unizar.es/record/60404/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:60404 articulos driver 2019-07-09-12:00:00 ARTICLE