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Screening and identifying potent OCT2 inhibitors with little toxicity in natural products in reducing OCT2\u2010mediated AKI is of great value. Flavonoids are enriched in various vegetables, fruits, and herbal products, and some were reported to produce transporter\u2010mediated drug\u2013drug interactions. This study aimed to screen potential inhibitors of OCT2 from 96 flavonoids, assess the nephroprotective effects on cisplatin\u2010induced kidney injury, and clarify the structure\u2013activity relationships of flavonoids with OCT2. Ten flavonoids exhibited significant inhibition (&gt;50%) on OCT2 in OCT2\u2010HEK293 cells. Among them, the six most potent flavonoid inhibitors, including pectolinarigenin, biochanin A, luteolin, chrysin, 6\u2010hydroxyflavone, and 6\u2010methylflavone markedly decreased cisplatin\u2010induced cytotoxicity. 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Thus, our findings would pave the way to predicting the potential risks of flavonoid\u2010containing food\/herb\u2013drug interactions in humans and optimizing flavonoid structure to alleviate OCT2\u2010related AKI.<\/jats:p>","DOI":"10.1002\/jat.4474","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T06:28:37Z","timestamp":1681453717000},"page":"1421-1435","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Inhibitory interaction of flavonoids with organic cation transporter 2 and their structure\u2013activity relationships for predicting nephroprotective effects"],"prefix":"10.1002","volume":"43","author":[{"given":"Huixin","family":"Tan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing Key Laboratory of Non\u2010Clinical Drug Metabolism and PK\/PD study, Beijing Key Laboratory of Active Substances 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