Abstract:
: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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
San José-Enériz E,Agirre X,Rabal O,Vilas-Zornoza A,Sanchez-Arias JA,Miranda E,Ugarte A,Roa S,Paiva B,Estella-Hermoso de Mendoza A,Alvarez RM,Casares N,Segura V,Martín-Subero JI,Ogi FX,Soule P,Santiveri CM,Campos-Olivasdoi
10.1038/ncomms15424subject
Has Abstractpub_date
2017-05-26 00:00:00pages
15424issn
2041-1723pii
ncomms15424journal_volume
8pub_type
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