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Reactive metabolites and related electrophilic drugs are among the most challenging small molecules to study. Conventional approaches to deconstruct the mode of action (MOA) of such molecules leverage bulk treatment of experimental specimens with an excess ...
Keap1 is associated with cytoprotective signaling. These roles of Keap1 typically focus on its role as a degrader of the antioxidant response (AR) transcription factor, Nrf2, and the inhibition of this process upon Keap1 labeling by electrophiles. However, ...
Weinheim2023
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Studying electrophile signaling is marred by difficulties in parsing changes in pathway flux attributable to on-target, vis-& agrave;-vis off-target, modifications. By combining bolus dosing, knockdown, and Z- REX & mdash;a tool investigating on- target/on ...
eLIFE SCIENCES PUBL LTD2022
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The mechanism-of-action of many electrohilic drugs remains poorly understood. Here, the authors use a redox-targeting approach to elucidate the basis for the innate immune cell toxicity of dimethyl fumarate, showing that it modifies Keap1 to trigger mitoch ...
In this tutorial review, we compare and contrast the chemical mechanisms of electrophile/oxidant sensing, and the molecular mechanisms of signal propagation. We critically analyze biological systems in which these different pathways are believed to be mani ...
