Journal article
Inhibition of histone demethylases LSD1 and UTX regulates ERα signaling in breast cancer
R Benedetti, C Dell’aversana, T De Marchi, D Rotili, NQ Liu, B Novakovic, S Boccella, S Di Maro, S Cosconati, A Baldi, E Niméus, J Schultz, U Höglund, S Maione, C Papulino, U Chianese, F Iovino, A Federico, A Mai, HG Stunnenberg Show all
Cancers | MDPI | Published : 2019
Open access
Abstract
In breast cancer, Lysine-specific demethylase-1 (LSD1) and other lysine demethylases (KDMs), such as Lysine-specific demethylase 6A also known as Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), are co-expressed and co-localize with estrogen receptors (ERs), suggesting the potential use of hybrid (epi)molecules to target histone methylation and therefore regulate/redirect hormone receptor signaling. Here, we report on the biological activity of a dual-KDM inhibitor (MC3324), obtained by coupling the chemical properties of tranylcypromine, a known LSD1 inhibitor, with the 2OG competitive moiety developed for JmjC inhibition. MC3324 displays unique features not exhibited ..
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Awarded by European Commission
Funding Acknowledgements
This research was funded by Blueprint 282510; MIUR20152TE5PK; EPICHEMBIO CM1406; EPIGEN-MIUR-CNR; AIRC-17217; VALERE: Vanvitelli per la Ricerca; Campania Regional Government Technology Platform Lotta alle Patologie Oncologiche: iCURE; Campania Regional Government FASE2: IDEAL. MIUR, Proof of Concept POC01_00043.