Having established our ECAL technology as a robust approach for target identification, chemoproteomic profiling of two structurally similar tertiary amine (TA) pharmacophores, SR9009 and SR9011 was pursued. These compounds were initially developed at Scripps as synthetic agonists of transcription factors REV-ERBα and REV-ERBβ for the regulation of circadian rhythm, and have attracted further interest for their involvement in a number of important cell functions through suspected REV-ERB interactions. This is due, in part, to the connection of REV-ERB to biological processes under control of the circadian cycle that includes immunological and metabolic pathways. In an in vivo study, cellular treatment with SR9009 was linked to REV-ERBα-mediated boosting of exercise capacity via increased mitochondrial production in skeletal muscle. This observation has led to the illicit usage of these SR9009-based agonists as exercise supplements and performance-enhancers within the body-building community. 40 SR9009 and SR9011 have also shown the ability to effect other biological processes that include the negative regulation of proinflammatory Th17 cell-mediated autoimmunity and tumor cell killing, all presumably through REV-ERB modulation. However, despite the illicit use in humans and the multiple in vitro and in vivo based activities of SR9009 and SR9011, direct identification of REV-ERB as the protein target is lacking. Thus, we set out to validate REV-ERB binding of these important biologically relevant molecules via chemoproteomic analysis using our ECAL technology.