2026-06-07T02:40:25Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/48812021-11-10T09:38:19Zcom_10259_3924com_10259_5086com_10259_2604col_10259_3925

00925njm 22002777a 4500 dc Kotev, Martin . author Manuel Manresa, Pilar . author Hernando Santa Cruz, Elsa author Soto Cerrato, Vanessa author Orozco, Modesto . author Quesada Pato, Roberto author Pérez Tomás, Ricardo author Guallar, Victor author 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. 1549-9596 http://hdl.handle.net/10259/4881 10.1021/acs.jcim.7b00178 Inhibition of human enhancer of zeste homolog 2 with tambjamine analogs