Drug-metabolizing enzymes and transporters (DMETs) (DMETs)

Drug-metabolizing enzymes and transporters (DMETs) are a comprehensive group of proteins that govern the pharmacokinetics and pharmacodynamics of most therapeutic agents [1, 7]. This category includes Phase I enzymes like Cytochrome P450s that modify drugs through oxidation, Phase II enzymes such as UGTs that conjugate them for excretion, and membrane transporters like P-glycoprotein that regulate cellular entry and exit [4, 5]. While DMETs are rarely the primary intended targets for treating a disease, they are critical "ADME targets" that determine a drug's systemic exposure, half-life, and safety profile [2, 8]. Genetic variations in these proteins, such as polymorphisms in CYP2D6 or SLCO1B1, are major drivers of inter-individual differences in drug efficacy and toxicity, making them central to the field of precision medicine [3, 5]. Furthermore, DMETs are the primary mediators of drug-drug interactions, where the modulation of their activity by one drug can lead to dangerous changes in the concentration of another [9, 10]. Understanding the interplay between these enzymes and transporters is essential for drug development and clinical management to avoid adverse reactions and ensure therapeutic success [1, 12].

Other names

ADME proteinsXenobiotic-metabolizing enzymes and transportersPhase I and II enzymes and transportersDrug metabolism and transport system

DMETs facilitate drug disposition through Phase I functionalization (oxidation, reduction, hydrolysis), Phase II conjugation (glucuronidation, sulfation, acetylation), and active or passive transport (efflux and uptake) across biological membranes [2, 4, 7].