Hydroxynaphthalenecarboxamides and substituted piperazinylpropandiols, two new series of BRAF inhibitors. A theoretical and experimental study

0534773 - ÚVGZ 2021 RIV US eng J - Journal Article
Campos, L. E. - Garibotto, F. - Angelina, E. - Kos, J. - Gonec, T. - Marvanová, P. - Vettorazzi, M. - Oravec, Michal - Jendrzejewska, I. - Jampílek, J. - Alvarez, S. E. - Enriz, R. D.
Hydroxynaphthalenecarboxamides and substituted piperazinylpropandiols, two new series of BRAF inhibitors. A theoretical and experimental study.
Bioorganic Chemistry. Roč. 103, OCT (2020), č. článku 104145. ISSN 0045-2068. E-ISSN 1090-2120
R&D Projects: GA MŠMT(CZ) EF16_019/0000797
Institutional support: RVO:86652079
Keywords : raf inhibitors * mapk pathway * BRAF inhibitors * Melanoma * Molecular modeling * Cell viability * ERK phosphorylation
OECD category: Biochemistry and molecular biology
Impact factor: 5.275, year: 2020
Method of publishing: Limited access
https://www.sciencedirect.com/science/article/pii/S0045206820314425?via%3Dihub

The oncogenic mutated kinase BRAF(V600E) is an attractive molecular target because it is expressed in several human cancers, including melanoma. To present, only three BRAF small inhibitors are approved by the FDA for the treatment of patients with metastatic melanoma: Vemurafenib, Dabrafenib and Encorafenib. Although many protocol treatments have been probed in clinical trials, BRAF inhibition has a limited effectiveness because patients invariably develop resistance and secondary toxic effects associated with the therapy. These limitations highlight the importance of designing new and better inhibitors with different structures that could establish different interactions in the active site of the enzyme and therefore decrease resistance progress.
Permanent Link: http://hdl.handle.net/11104/0312945