Special Section on New Era of Transporter Science: Unraveling the Functional Role of Orphan Transporters-Minireview Transcriptional Regulation of Solute Carrier Drug Transporters

Facilitated transport is necessitated for large size, charged, and/or hydrophilic drugs to move across the membrane. The drug trans-porters in the solute carrier (SLC) superfamily, mainly including organic anion-transporting polypeptides, organic anion transporters, organic cation transporters, organic cation/carnitine transporters, peptide transporters, and multidrug and toxin extrusion proteins, are critical facilitators of drug transport and distribution in human body. The expression of these SLC drug transporters is found in tissues throughout the body, with high abundance in the epithelial cells of major organs for drug disposition such as intestine, liver, and kidney. These SLC drug transporters are clinically important in drug absorption, metabolism, distribution, and excretion. The mechanisms underlying their regulation have been revealing in recent years. Epigenetic and nuclear receptor-mediated transcriptional regulation of SLC drug transporters has particularly attracted much attention. This review focuses on the transcriptional regulation of major SLC drug transporter genes. Revealing the mechanisms underlying the transcription of these critical drug transporters will help us understand pharmacokinetics and pharmacodynamics, ultimately improving drug therapeutic effectiveness while minimizing drug toxicity. SIGNIFICANCE STATEMENT It has become increasingly recognized that solute carrier drug trans-porters play a crucial and sometimes determinative role in drug dis-position and response, which is reflected in decision making during not only clinical drug therapy but also drug development. Under-standing the mechanisms accounting for the transcription of these transporters is critical to interpret their abundance in various tis-sues under different conditions, which is necessary to clarify the pharmacological response, adverse effects, and drug-drug interactions for clinically used drugs.

Automated summary

Facilitated transport is necessary for large size, charged, and/or hydrophilic drugs to cross the membrane. SLC drug transporters play crucial roles in drug transport and distribution in the human body, with high expression in major organs like the intestine, liver, and kidney. Understanding the transcriptional regulation of these critical drug transporters is essential for interpreting pharmacokinetics, pharmacodynamics, and improving drug therapeutic effectiveness.