Long, Marcus J. C.Herrera, Pierre A. MirandaAye, Yimon2022-08-012022-08-012022-08-012022-04-0810.1021/acs.chemrestox.2c00006https://infoscience.epfl.ch/handle/20.500.14299/189622WOS:000825019100001Our bodies produce a host of electrophilic species that can label specific endogenous proteins in cells. The signaling roles of these molecules are under active debate. However, in our opinion, it is becoming increasingly likely that electrophiles can rewire cellular signaling processes at endogenous levels. Attention is turning more to understanding how nuanced electrophile signaling in cells is. In this Perspective, we describe recent work from our laboratory that has started to inform on different levels of context-specific regulation of proteins by electrophiles. We discuss the relevance of these data to the field and to the broader application of electrophile signaling to precision medicine development, beyond the traditional views of their pleiotropic cytotoxic roles.Chemistry, MedicinalChemistry, MultidisciplinaryToxicologyPharmacology & PharmacyChemistryplacebo-controlled phase-3dimethyl fumaratetyrannosaurus-rexoxidative stressoral bg-12in-vitrop-tefbproteinelongationredoxHitting the Bullseye: Endogenous Electrophiles Show Remarkable Nuance in Signaling Regulationtext::journal::journal article::research article