RT info:eu-repo/semantics/article
T1 Inhibition of human enhancer of zeste homolog 2 with tambjamine analogs
A1 Kotev, Martin .
A1 Manuel Manresa, Pilar .
A1 Hernando Santa Cruz, Elsa
A1 Soto Cerrato, Vanessa
A1 Orozco, Modesto .
A1 Quesada Pato, Roberto
A1 Pérez Tomás, Ricardo
A1 Guallar, Victor
K1 Química orgánica
K1 Chemistry, Organic
AB 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.
PB American Chemical Society
SN 1549-9596
YR 2017
FD 2017-08
LK http://hdl.handle.net/10259/4881
UL http://hdl.handle.net/10259/4881
LA eng
NO SpanishGovernment (CTQ2016-79138-R; FIS PI13/00089), theConsejeríade Educación de la Junta de Castilla y León(Projects BU340U13 and BU092U16), and from La MaratódeTV3 Foundation (20132730).
DS Repositorio Institucional de la Universidad de Burgos
RD 25-abr-2024