Pomalidomide hybrids act as proteolysis targeting chimeras: Synthesis, anticancer activity and B-Raf degradation.
Bioorg Chem
; 87: 191-199, 2019 06.
Article
em En
| MEDLINE
| ID: mdl-30901674
ABSTRACT
As the first intracellular signaling molecule and the most frequently mutated oncogene, B-Raf represents an important target in cancer therapy. Here we report several pomalidomide hybrids acting as proteolysis targeting chimeras (PROTACs) for the degradation of B-Raf. Due to its high expression of B-Raf, MCF-7 cells are sensitive to these compounds. Among them, compound 2 can effectively kill cancer cells via inducing cells apoptosis. As a B-Raf degrader, compound 2 can accelerate the degradation of B-Raf by recruiting ubiquitin-proteasome system, and further affects the expression of Mcl-1, a downstream protein of B-Raf. The anticancer mechanism of compound 2 is quite different from its mother compound and cancer cells seem to be more sensitive to the degrader, hinting that degradation of B-Raf by PROTAC is a potential way for cancer treatment.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Talidomida
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Proteínas Proto-Oncogênicas B-raf
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Inibidores de Proteínas Quinases
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Proteólise
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Antineoplásicos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article