Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions

Pyrethroids are highly potent insecticides used worldwide in ∼3,500 registered products to control diseases spread by arthropods. Although they are critical for controlling a diverse spectrum of diseases, such intense exposure affects health and drives the rapid evolution of insecticide resistance. Here we have developed a suite of pyrethroid mimetic activity-based probes (PyABPs) to selectively label and identify P450s associated with pyrethroid metabolism in highly divergent organisms. Using a rat liver model, we demonstrate that PyABPs detect pyrethroid metabolizing P450s and a network of drug-metabolizing enzymes that is termed the "pyrethrome." This discovery has broad scientific interest and provides a unique perspective on insecticide interactions, improving understanding of insecticide metabolism and aiding the development of tools for disease control.