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The transcription factor NF-E2 p45-related factor 2 (NRF2; encoded by NFE2L2) and its principal negative regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (KEAP1), are critical in the maintenance of redox, metabolic and protein homeostasis, as well as the regulation of inflammation. Thus, NRF2 activation provides cytoprotection against numerous pathologies including chronic diseases of the lung and liver; autoimmune, neurodegenerative and metabolic disorders; and cancer initiation. One NRF2 activator has received clinical approval and several electrophilic modifiers of the cysteine-based sensor KEAP1 and inhibitors of its interaction with NRF2 are now in clinical development. However, challenges regarding target specificity, pharmacodynamic properties, efficacy and safety remain.
This article was published in the following journal.
Name: Nature reviews. Drug discovery
The Keap1-Nrf2-ARE system serves as a premier defence mechanism to curb oxidative stress, which remains as one of the major causes of ageing and pathogenesis in various diseases. Nrf2 is the principal...
Keap1, Kelch-like erythroid derived Cap 'n' collar homology (ECH) associated protein 1 is a highly redox-sensitive member of the BTB-Kelch substrate adaptor protein which acts as a major upstream regu...
The transcription factor NF-E2 Related Factor-2 (NRF2) is an important drug target. Activation of NRF2 has chemopreventive effects in cancer and exerts beneficial effects in a number of diseases, incl...
Nrf2, a master regulator of the phase II gene response to stress, is kept at low concentrations in the cell through binding to Keap1, an adaptor protein for the Cul3 ubiquitin ligase complex. To ident...
The KEAP1 (Kelch-like ECH-associated protein 1)-NRF2 (NF-E2-related factor 2) system controls the biochemical defense activity against agents toxic to mammals and responds to exogenous and endogenous ...
Oxidative stress and inflammation are cardiovascular risk factors in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). Nuclear transcription factors play roles in th...
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Collaborations in biotechnology
Commercial and academic collaborations are used throughout the biotechnology and pharmaceutical sector to enhance research and product development. Collaborations can take the form of research and evaluation agreements, licensing, partnerships etc. ...
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