Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism.
Bioorg Med Chem
; 21(14): 4011-9, 2013 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-23647822
ABSTRACT
Keap1 binds to the Nrf2 transcription factor to promote its degradation, resulting in the loss of gene products that protect against oxidative stress. While cell-active small molecules have been identified that modify cysteines in Keap1 and effect the Nrf2 dependent pathway, few act through a non-covalent mechanism. We have identified and characterized several small molecule compounds that specifically bind to the Keap1 Kelch-DC domain as measured by NMR, native mass spectrometry and X-ray crystallography. One compound upregulates Nrf2 response genes measured by a luciferase cell reporter assay. The non-covalent inhibition strategy presents a reasonable course of action to avoid toxic side-effects due to non-specific cysteine modification.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Péptidos y Proteínas de Señalización Intracelular
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Factor 2 Relacionado con NF-E2
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Bibliotecas de Moléculas Pequeñas
Tipo de estudio:
Prognostic_studies
Idioma:
En
Año:
2013
Tipo del documento:
Article