T-REX electrophile toolbox enables assessment of downstream signaling strength triggered by target-specific delivery of specific bioactive LDEs (1–10) to specific proteins in cells (e.g., Keap1) at a precise time. Inset: The simplified model for Nrf2–ARE pathway. The downstream phenotypic responses—Nrf2 stabilization and ARE upregulation—are observed from whole-cell LDE flooding. Electrophilic modifications of various upstream redox-sensitive targets, including Keap1, PTEN, Akt, GSK3, PKC, etc., have been implicated to play roles in modulating Nrf2–ARE signaling. Using T-REX, this study directly probes the Nrf2–ARE signaling strength selectively elicited by LDE-signal-specific and Keap1-protein-specific electrophilic modifications in an otherwise unmodified proteome.