A novel β-TrCP1/NRF2 interaction inhibitor for effective anti-inflammatory therapy
[Background] Non-communicable chronic diseases are characterized by low-grade inflammation and oxidative stress. Extensive research has identified the transcription factor NRF2 as a potential therapeutic target. Current NRF2 activators, designed to inhibit its repressor KEAP1, often exhibit undesira...
| Autores: | , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/413124 |
| Acceso en línea: | http://hdl.handle.net/10261/413124 |
| Access Level: | acceso abierto |
| Palabra clave: | NRF2 β-TrCP1 Protein–protein interaction-inhibitor Inflammation Liver |
| Sumario: | [Background] Non-communicable chronic diseases are characterized by low-grade inflammation and oxidative stress. Extensive research has identified the transcription factor NRF2 as a potential therapeutic target. Current NRF2 activators, designed to inhibit its repressor KEAP1, often exhibit undesirable side effects. As an alternative approach, we previously developed PHAR, a protein–protein interaction inhibitor of β-TrCP1/NRF2, which promotes NRF2 activation. Using the same in silico screening platform, we have now identified a novel compound, P10. This small molecule selectively interferes with the β-TrCP1/NRF2 interaction, leading to NRF2 stabilization and transcriptional activation of its target genes in a β-TrCP1-dependent manner, demonstrating promising effects in a liver model of acute inflammation. |
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