In our previous unbiased chemical screen, we identified NOB, along with its close analog tangeretin, as a clock-enhancing small molecule in cell-based circadian reporter assays.172 Focusing on NOB, we demonstrated a circadian clock-dependent efficacy to blunt obesity and metabolic dysfunction in mouse models, and importantly identified RORα and RORγ as its direct targetsvia radioactive ligand binding assays. Here, CLOCK is linked to obesity due to melanocortin 4 receptor deficiency.