With the desired TA-DZE probe in hand, chemoproteomic analysis using ECAL was performed in HEK293T cells overexpressing REV-ERBα, the reported target of this molecular scaffold (Figure and Figure ). Accordingly, HEK293T-REV-ERBα cells were incubated with TA-DZE probe 21 with or without electrolysis. Following the electrochemical treatment step, labeled proteins were then conjugated to biotin-azide through CuAAC click reaction and affinity purified on streptavidin beads. Enriched proteins were subjected to tryptic digestion and downstream TMTbased quantitative LC-MS/MS analysis. Volcano plot analysis identified proteins from our ECAL method showing significant enrichment over the no electrolysis controls (Figure ). Gene ontology (GO) analysis of the detected proteins showed enrichment of biological terms associated with both SR9009/SR9011 and REV-ERB activity that include metabolic and gene expression processes (Figure ). However, to our surprise, REV-ERBα was not enriched with our TA-DZE probe 21 despite overexpression of this protein in 293T cells (Figure and Figure ). This result, in conjunction with a recent study reporting that SR9009 modulates cellular metabolism, viability, proliferation, and gene expression in REV-ERB knockout systems, suggests that these TA scaffolds potentially operate independently of REV-ERB.