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We investigated the ability of bioactive compounds to chemically prime plants for flooding events. A high-throughput chemical genetic screen of 2,237 bioactive molecules was performed using an Arabidopsis thaliana luciferase-based reporter line driven by the ALCOHOL DEHYDROGENASE promoter, a hypoxia-inducible gene involved in anaerobic metabolism. The screen identified chlorquinaldol (CQD), an 8-hydroxyquinoline derivative, as a potent inducer of hypoxia responses. CQD inhibits the activity of PLANT CYSTEINE OXIDASES (PCOs), which are crucial oxygen-sensing enzymes in plants, resulting in the stabilization of the ETHYLENE RESPONSE FACTOR type VII and activation of hypoxia-responsive transcription under normoxic conditions. Plants pretreated with CQD showed enhanced tolerance to waterlogging and submergence, indicating that chemical priming of hypoxia responses improves plant tolerance to flooding. This study demonstrates that chemical inhibition of PCOs is an effective strategy for priming hypoxia responses and improving flooding tolerance in plants.<\/jats:p>","DOI":"10.1093\/plphys\/kiag505","type":"journal-article","created":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T11:39:33Z","timestamp":1783856373000},"source":"Crossref","is-referenced-by-count":1,"title":["Chemical priming of hypoxia responses via PLANT CYSTEINE OXIDASE inhibition improves flooding tolerance"],"prefix":"10.1093","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4911-7778","authenticated-orcid":false,"given":"Francesco","family":"Fioriti","sequence":"first","affiliation":[{"name":"Institute of Plant Sciences, Sant\u2019Anna School of Advanced Studies , Via Guidiccioni 10, San Giuliano Terme, Pisa 56010 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5191-9397","authenticated-orcid":false,"given":"Rocco 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