{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:45:44Z","timestamp":1792802744263,"version":"4.5.0"},"reference-count":75,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010883","name":"Scientific Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine","doi-asserted-by":"publisher","award":["20261216"],"award-info":[{"award-number":["20261216"]}],"id":[{"id":"10.13039\/501100010883","id-type":"DOI","asserted-by":"publisher"}]},{"award":["20261216"],"award-info":[{"award-number":["20261216"]}],"id":[{"id":"https:\/\/ror.org\/05vkkzf98","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Guangdong Academy of Medical Sciences","award":["B2025064"],"award-info":[{"award-number":["B2025064"]}]},{"award":["B2025064"],"award-info":[{"award-number":["B2025064"]}],"id":[{"id":"https:\/\/ror.org\/0432p8t34","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2025A1515012608"],"award-info":[{"award-number":["2025A1515012608"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2014especially regarding in vivo phase II metabolism\u2014remain unclear. This review integrates recent cryogenic electron microscopy (cryo-EM) structural biology and transporter kinetics to delineate the molecular basis of flavonoid\u2013OAT 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 \u201cdouble-edged\u201d toxicological effect: high-affinity OAT inhibition risks herb\u2013drug 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.<\/jats:p>","DOI":"10.3390\/ijms27073310","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T08:09:00Z","timestamp":1775549340000},"page":"3310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Flavonoid Interactions with Renal Organic Anion Transporters OAT1 and OAT3: Structure\u2013Activity Relationships and Clinical Implications"],"prefix":"10.3390","volume":"27","author":[{"given":"Kai","family":"Tong","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinmao","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6657-5059","authenticated-orcid":false,"given":"Kazuko","family":"Kaneda-Nakashima","sequence":"additional","affiliation":[{"name":"Institute for Radiation Sciences, The University of Osaka, 2-4 Yamadaoka, Suita 565-0871, Japan"},{"name":"Core for Medicine and Science Collaborative Research and Education, Forefront Research Center, Graduate School of Science, The University of Osaka, 1-1 Machikaneyama, Toyonaka 560-0043, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6633-6410","authenticated-orcid":false,"given":"Ling","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rana, J.N., and Mumtaz, S. 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