Fluorescent dyes as functional probes for studying drug-transporting solute carriers

Solute carrier (SLC) transporters are key players in drug pharmacokinetics and are notably involved in drug-drug interactions; their potential interactions with new molecular entities must be evaluated during pharmaceutical development for regulatory purposes.Various fluorescent probes substrates for SLCs have been characterised. This review summarises the nature of these dyes and their application <i>in vitro</i> for investigating interactions between drugs or other chemicals and main 'regulatory' SLCs that handle anionic or cationic compounds. The advantages and limitations of using fluorescent probes for SLC studies are discussed.Fluorescent probe-based SLC assays enable the identification and characterisation of xenobiotic-mediated inhibition of SLC activity through <i>cis</i>-inhibition assays. They also facilitate the study of fundamental properties, polymorphisms, and regulatory pathways of SLCs, as well as the characterisation of SLC substrates <i>via trans</i>-stimulation or competitive counterflow assays.Dye-based SLC activity assays are more cost-effective and less labour-intensive than conventional methods relying on radiolabeled substrates or liquid chromatography-tandem mass spectrometry. They are also fully compatible with high-throughput screening.Limitations of fluorescent dye-based SLC assays include the relatively low specificity of fluorescent probes, substrate-dependent variability in SLC inhibition, and limited performance of <i>trans</i>-stimulation or competitive counterflow assays for identifying SLC substrates.