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Off-target effects continue to impede disease interventions, particularly when targeting a specific protein within a family of similar proteins, such as kinase isoforms that play tumor-subtype-specific roles in cancers. Exploiting the specific electrophili ...
Here we discuss, how by applying chemical concepts to biological problems, methods have been developed to map spatiotemporal regulation of proteins and small-molecule modulation of proteome signaling responses. We outline why chemical-biology platforms are ...
2019
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Revolutionary proteomic strategies have enabled rapid profiling of the cellular targets of electrophilic small molecules. However, precise means to directly interrogate how these individual electrophilic modifications at low occupancy functionally reshape ...
2019
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Ability to faithfully report drug-target interactions constitutes a major critical parameter in preclinical/clinical settings. Yet the assessment of target engagement remains challenging, particularly for promiscuous and/or polypharmacologic ligands. Drawi ...
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 ...
The nuclear factor erythroid 2 related factor 2 (Nrf2) signaling axis is a target of covalent drugs and bioactive native electrophiles. However, much of our understanding of Nrf2 regulation has been focused at the protein level. Here we report a post-trans ...
