2026-04-29T04:08:50Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/68832024-11-29T16:28:14Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
San José-Enériz, Edurne
author
Agirre, Xabier
author
Rabal, Obdulia
author
Vilas-Zornoza, Amaia
author
Sanchez-Arias, Juan A
author
Miranda, Estibaliz
author
Ugarte, Ana
author
Roa, Sergio
author
Paiva, Bruno
author
Estella-Hermoso de Mendoza, Ander
author
Alvarez, Rosa María
author
Casares, Noelia
author
Segura, Victor
author
Martín-Subero, José I
author
Ogi, François-Xavier
author
Soule, Pierre
author
Santiveri, Clara M
author
Campos-Olivas, Ramón
author
Castellano, Giancarlo
author
García Fernández de Barrena, Maite
author
Rodríguez-Madoz, Juan Roberto
author
García-Barchino, Maria José
author
Lasarte, Juan Jose
author
Avila, Matias A
author
Martinez-Climent, Jose Angel
author
Oyarzabal, Julen
author
Prosper, Felipe
funder
Instituto de Salud Carlos III
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación La Marató TV3
funder
Centro de Investigación Biomedica en Red - CIBER
2018-12-18T12:06:13Z
2018-12-18T12:06:13Z
2017
Nat Commun. 2017; 8: 15424.
2041-1723
http://hdl.handle.net/20.500.12105/6883
28548080
10.1038/ncomms15424
2041-1723
Nature communications
The 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.
eng
Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies
journal article
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