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dc.contributor.authorSan José-Enériz, Edurne
dc.contributor.authorAgirre, Xabier
dc.contributor.authorRabal, Obdulia
dc.contributor.authorVilas-Zornoza, Amaia
dc.contributor.authorSanchez-Arias, Juan A
dc.contributor.authorMiranda, Estibaliz
dc.contributor.authorUgarte, Ana
dc.contributor.authorRoa, Sergio
dc.contributor.authorPaiva, Bruno
dc.contributor.authorEstella-Hermoso de Mendoza, Ander
dc.contributor.authorAlvarez, Rosa María
dc.contributor.authorCasares, Noelia
dc.contributor.authorSegura, Victor
dc.contributor.authorMartín-Subero, José I
dc.contributor.authorOgi, François-Xavier
dc.contributor.authorSoule, Pierre
dc.contributor.authorSantiveri, Clara M
dc.contributor.authorCampos Olivas, Ramón 
dc.contributor.authorCastellano, Giancarlo
dc.contributor.authorde Barrena, Maite Garcia Fernandez
dc.contributor.authorRodriguez-Madoz, Juan Roberto
dc.contributor.authorGarcía-Barchino, Maria José
dc.contributor.authorLasarte, Juan Jose
dc.contributor.authorAvila, Matias A
dc.contributor.authorMartinez-Climent, Jose Angel
dc.contributor.authorOyarzabal, Julen
dc.contributor.authorProsper, Felipe
dc.date.accessioned2018-12-18T12:06:13Z
dc.date.available2018-12-18T12:06:13Z
dc.date.issued2017
dc.identifier.citationNat Commun. 2017; 8: 15424.es_ES
dc.identifier.issn2041-1723es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6883
dc.description.abstractThe indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favoured development of epigenetic drugs. In this study, we design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of haematological neoplasia (acute myeloid leukaemia-AML, acute lymphoblastic leukaemia-ALL and diffuse large B-cell lymphoma-DLBCL) with the lead compound CM-272, inhibits cell proliferation and promotes apoptosis, inducing interferon-stimulated genes and immunogenic cell death. CM-272 significantly prolongs survival of AML, ALL and DLBCL xenogeneic models. Our results represent the discovery of first-in-class dual inhibitors of G9a/DNMTs and establish this chemical series as a promising therapeutic tool for unmet needs in haematological tumours.es_ES
dc.description.sponsorshipWe particularly acknowledge the Biobank of the University of Navarra for its collaboration. We thank Dr Edorta Martínez de Marigorta and Dr Francisco Palacios from Departamento de Química Orgánica I, Facultad de Farmacia, Universidad del Pais Vasco for 13C NMR determination and Angel Irigoyen Barrio and Dr Ana Romo Hualde, from University of Navarra, for HRMS determination. Dr. Irene de Miguel Turrullols from Small Molecule Discovery Platform, CIMA, University of Navarra is acknowledged for NMR data interpretation. This work was funded by grants from Instituto de Salud Carlos III (ISCIII) PI10/01691, PI13/01469, PI14/01867, PI10/2983, TRASCAN (EPICA), CIBERONC, cofinanciacion FEDER, RTICC RD12/0036/0068, Fundació La Marató de TV3 (20132130-31-32) and ‘Fundación Fuentes Dutor’. B.P. is supported by a Sara Borrell fellowship CD13/00340 and X.A. is a Marie Curie researcher under contract ‘LincMHeM-330598’.es_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Groupes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshAnimals es_ES
dc.subject.meshAntineoplastic Agents es_ES
dc.subject.meshApoptosis es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshCell Proliferation es_ES
dc.subject.meshCrystallography, X-Ray es_ES
dc.subject.meshDNA Modification Methylases es_ES
dc.subject.meshDose-Response Relationship, Druges_ES
dc.subject.meshDrug Evaluation, Preclinical es_ES
dc.subject.meshEnzyme Inhibitors es_ES
dc.subject.meshEpigenesis, Genetices_ES
dc.subject.meshFemale es_ES
dc.subject.meshHematologic Neoplasms es_ES
dc.subject.meshHistocompatibility Antigens es_ES
dc.subject.meshHistone-Lysine N-Methyltransferase es_ES
dc.subject.meshHumans es_ES
dc.subject.meshInterferons es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Inbred BALB C es_ES
dc.subject.meshMicrosomes, Liver es_ES
dc.subject.meshMolecular Docking Simulation es_ES
dc.subject.meshSurvival Analysis es_ES
dc.subject.meshTreatment Outcome es_ES
dc.subject.meshXenograft Model Antitumor Assays es_ES
dc.subject.meshDrug Design es_ES
dc.titleDiscovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancieses_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID28548080es_ES
dc.format.volume8es_ES
dc.format.page15424es_ES
dc.identifier.doi10.1038/ncomms15424es_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderEuropean Regional Development Fund (ERDF/FEDER)es_ES
dc.contributor.funderFundación La Mataró TV3es_ES
dc.contributor.funderCentro de Investigación Biomedica en Red - CIBERes_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn2041-1723es_ES
dc.relation.publisherversionhttps://doi.org/ 10.1038/ncomms15424.es_ES
dc.identifier.journalNature communicationses_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Espectroscopía y RMNes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI10/01691es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI13/01469es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI14/01867es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI10/2983es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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