Rational Design of a Two?Photon Fluorescent Probe for Human Cytochrome P450 3A and the Visualization of Mechanism?Based Inactivation

Mechanism-based inactivation (MBI) can mediate adverse reactions and hepatotoxicity from drugs, which is a result of their conversion into highly reactive metabolites catalyzed by enzymes such as cytochrome P450 3A (CYP3A). In the present research, we optimized key interaction domain fluorophore with target protein to develop two-photon fluorescent probe for CYP3A that involved in metabolism more than half all clinical drugs. The developed BN-1 exhibited appropriate selectivity sensitivity semi-quantitative detection imaging endogenous activity various living systems, thereby providing high-throughput screening system enabling evaluation MBI-associated CYP3A. Using molecular tool facilitates efficient discovery characterization CYP3A-induced MBI natural systems.