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Updated: Apr 15, 2026

Isolation of Primary Human Proximal Tubule Epithelial Cells and Their Use in Creating a Microphysiological Model of the Renal Proximal Tubule
Published on: May 9, 2025
Flavonoid Interactions with Renal Organic Anion Transporters OAT1 and OAT3: Structure-Activity Relationships and
Kai Tong1, Pinmao Ye1, Kazuko Kaneda-Nakashima2,3
1School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Abstract:
Renal organic anion transporters 1 (OAT1) and 3 (OAT3) mediate the excretion of endogenous metabolites and xenobiotics. Flavonoids interact significantly with these transporters, but the structural determinants-especially regarding in vivo phase II metabolism-remain unclear. This review integrates recent cryogenic electron microscopy (cryo-EM) structural biology and transporter kinetics to delineate the molecular basis of flavonoid-OAT interactions. We highlight phase II metabolites as key in vivo effectors. Structurally, OAT1 strictly favors compact, planar anionic scaffolds, whereas OAT3 accommodates bulkier, conjugated forms. Crucially, flavonoids exert a "double-edged" toxicological effect: high-affinity OAT inhibition risks herb-drug interactions, yet competitively limits the tubular uptake of nephrotoxins. Furthermore, disease states and post-translational regulation reshape these interactions. By bridging structural insights with biomarker-guided pharmacokinetics, we propose a mechanistic framework to improve the precise safety assessment of flavonoid-containing therapeutics.
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