2026-04-28T08:53:53Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/48812021-11-10T09:38:19Zcom_10259_3924com_10259_5086com_10259_2604col_10259_3925
Kotev, Martin .
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500
Manuel Manresa, Pilar .
0e8b3cef-7ea1-44a8-af01-7b49c8f0e385
500
Hernando Santa Cruz, Elsa
279
500
Soto Cerrato, Vanessa
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500
Orozco, Modesto .
f7613a29-b440-4aa8-a604-dfedb5adccb0
500
Quesada Pato, Roberto
458
500
Pérez Tomás, Ricardo
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500
Guallar, Victor
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500
2018-08-24T09:48:45Z
2018-08-24T09:48:45Z
2017-08
1549-9596
http://hdl.handle.net/10259/4881
10.1021/acs.jcim.7b00178
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.
Spanish
Government (CTQ2016-79138-R; FIS PI13/00089), the
Consejería
de Educación de la Junta de Castilla y León
(Projects BU340U13 and BU092U16), and from La Maratóde
TV3 Foundation (20132730).
application/pdf
eng
American Chemical Society
Journal of Chemical Information and Modeling. 2017, V. 57, n. 8, p. 2089-2098
https://doi.org/10.1021/acs.jcim.7b00178
info:eu-repo/grantAgreement/MICINN/CTQ2016-79138-R
info:eu-repo/grantAgreement/MSCBS/PI13-00089
info:eu-repo/grantAgreement/JCyL/BU340U13
info:eu-repo/grantAgreement/JCyL/BU092U16
info:eu-repo/grantAgreement/TV3Foundation/20132730
Química orgánica
Chemistry, Organic
Inhibition of human enhancer of zeste homolog 2 with tambjamine analogs
info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
info:eu-repo/semantics/openAccess
THUMBNAIL
Kotev-JCIM_ 2017.pdf.jpg
Kotev-JCIM_ 2017.pdf.jpg
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ORIGINAL
Kotev-JCIM_ 2017.pdf
Kotev-JCIM_ 2017.pdf
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https://riubu.ubu.es/bitstream/10259/4881/1/Kotev-JCIM_%202017.pdf
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LICENSE
license.txt
license.txt
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TEXT
Kotev-JCIM_ 2017.pdf.txt
Kotev-JCIM_ 2017.pdf.txt
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10259/4881
oai:riubu.ubu.es:10259/4881
2021-11-10 10:38:19.764
Repositorio Institucional de la Universidad de Burgos
bubrep@ubu.es
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