000060404 001__ 60404
000060404 005__ 20190709135526.0
000060404 0247_ $$2doi$$a10.1038/srep39732
000060404 0248_ $$2sideral$$a97889
000060404 037__ $$aART-2017-97889
000060404 041__ $$aeng
000060404 100__ $$aNeira, J.L.
000060404 245__ $$aIdentification of a Drug Targeting an Intrinsically Disordered Protein Involved in Pancreatic Adenocarcinoma
000060404 260__ $$c2017
000060404 5060_ $$aAccess copy available to the general public$$fUnrestricted
000060404 5203_ $$aIntrinsically 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.
000060404 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/CTQ2015-64445-R$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2013-47064-P$$9info:eu-repo/grantAgreement/ES/FIS/PI15-00663$$9info:eu-repo/grantAgreement/ES/FIS/PI11-02578$$9info:eu-repo/grantAgreement/ES/FIS/PI10-00186$$9info:eu-repo/grantAgreement/ES/DGA/B89$$9info:eu-repo/grantAgreement/ES/DGA/B01
000060404 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000060404 590__ $$a4.122$$b2017
000060404 591__ $$aMULTIDISCIPLINARY SCIENCES$$b12 / 64 = 0.188$$c2017$$dQ1$$eT1
000060404 592__ $$a1.533$$b2017
000060404 593__ $$aMultidisciplinary$$c2017$$dQ1
000060404 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000060404 700__ $$aBintz, J.
000060404 700__ $$aArruebo, M.
000060404 700__ $$aRizzuti, B.
000060404 700__ $$aBonacci, T.
000060404 700__ $$0(orcid)0000-0002-1232-6310$$aVega, S.
000060404 700__ $$0(orcid)0000-0001-5932-2889$$aLanas, A.$$uUniversidad de Zaragoza
000060404 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, A.$$uUniversidad de Zaragoza
000060404 700__ $$aIovanna, J.L.
000060404 700__ $$0(orcid)0000-0001-5664-1729$$aAbián, O.$$uUniversidad de Zaragoza
000060404 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000060404 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000060404 773__ $$g7 (2017), [15 pp.]$$pSci. rep.$$tScientific reports$$x2045-2322
000060404 8564_ $$s1363982$$uhttps://zaguan.unizar.es/record/60404/files/texto_completo.pdf$$yVersión publicada
000060404 8564_ $$s107763$$uhttps://zaguan.unizar.es/record/60404/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000060404 909CO $$ooai:zaguan.unizar.es:60404$$particulos$$pdriver
000060404 951__ $$a2019-07-09-12:00:00
000060404 980__ $$aARTICLE