Searching for CAR modulators

The constitutive androstane receptor (CAR; NR1I3) has been established as one of the main drug- and xenobiotic-responsive transcriptional regulators, collectively called xenosensors. CAR activates the expression of several oxidative, hydrolytic, and conjugative drug-metabolizing enzymes and drug transporters, and therefore, it contributes to drug and xenobiotic elimination, drug interactions, and toxicological processes. This minireview introduces mechanisms that modulate CAR activity and focuses on the recent approaches used to search and characterize CAR agonists, inverse agonists, and indirect activators. This minireview is dedicated to Dr. Masahiko Negishi to celebrate his scientific achievements during his long service at the National Institutes of Health. ; final draft ; peerReviewed