2024-03-28T13:26:53Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/48812021-11-10T09:38:19Zcom_10259_3924com_10259_5086com_10259_2604col_10259_3925
Kotev, Martin .
Manuel Manresa, Pilar .
Hernando Santa Cruz, Elsa
Soto Cerrato, Vanessa
Orozco, Modesto .
Quesada Pato, Roberto
Pérez Tomás, Ricardo
Guallar, Victor
2017-08
Combining computational modeling, de novo compound synthesis, and in vitro and cellular assays, we have performed an inhibition study against the enhancer of zeste homolog 2 (EZH2) histone-lysine N-methyltransferase. This enzyme is an important catalytic component of the PRC2 complex whose alterations have been associated with different cancers. We introduce here several tambjamine-inspired derivatives with low micromolar in vitro activity that produce a significant decrease in histone 3 trimethylation levels in cancer cells. We demonstrate binding at the methyl transfer active site, showing, in addition, that the EZH2 isolated crystal structure is capable of being used in molecular screening studies. Altogether, this work provides a successful molecular model that will help in the identification of new specific EZH2 inhibitors and identify a novel class of tambjamine-derived EZH2 inhibitors with promising activities for their use in cancer treatment.
application/pdf
http://hdl.handle.net/10259/4881
eng
American Chemical Society
Inhibition of human enhancer of zeste homolog 2 with tambjamine analogs
info:eu-repo/semantics/article
TEXT
RIUBU. Repositorio Institucional de la Universidad de Burgos
Hispana