Searching for Constitutive Androstane Receptor Modulators

Area of Science:

• Pharmacology
• Toxicology
• Molecular Biology

Background:

• The constitutive androstane receptor (CAR; NR1I3) is a key xenosensor regulating drug and xenobiotic metabolism.
• CAR influences the expression of drug-metabolizing enzymes and transporters, impacting drug interactions and toxicity.
• Understanding CAR's role is vital for drug development and assessing xenobiotic effects.

Purpose of the Study:

• To review mechanisms modulating CAR activity.
• To introduce recent approaches for identifying and characterizing CAR modulators (agonists, inverse agonists, indirect activators).
• To discuss the significance of CAR modulator discovery for drug development and biological research.

Main Methods:

• Literature review of mechanisms controlling CAR activity.
• Focus on recent screening and characterization methods for CAR agonists, inverse agonists, and indirect activators.
• Discussion of essential features of identified CAR modulators.

Main Results:

• CAR activation leads to increased expression of drug-metabolizing enzymes and transporters.
• Various methods exist for discovering and characterizing CAR modulators.
• CAR modulators are valuable tools for studying CAR's biological functions.

Conclusions:

• Discovery and characterization of CAR modulators are essential for advancing drug development and toxicology.
• Effective methods for identifying CAR modulators are crucial for dissecting CAR's biological roles.
• This review provides insights into current strategies for CAR modulator research.