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The channel has wide\u2010ranging roles and is considered as a target for novel therapeutics in ailments spanning cancers and cardiovascular, dental, gastrointestinal, hepatobiliary, infectious, musculoskeletal, nervous system, ocular, pregnancy, renal, respiratory and urological disorders. The identification of PIEZO1 modulators is in its infancy but useful experimental tools emerged for activating, and to a lesser extent inhibiting, the channels. Elementary structure\u2013activity relationships are known for the Yoda series of small molecule agonists, which show the potential for diverse physicochemical and pharmacological properties. Intriguing effects of Yoda1 include the stimulated removal of excess cerebrospinal fluid. Despite PIEZO1's broad expression, opportunities are suggested for selective positive or negative modulation without intolerable adverse effects. Here we provide a focused, non\u2010systematic, narrative review of progress with this pharmacology and discuss potential future directions for research in the area.<\/jats:p>","DOI":"10.1111\/bph.17351","type":"journal-article","created":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T02:45:31Z","timestamp":1728960331000},"page":"4714-4732","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Pharmacology of PIEZO1 channels"],"prefix":"10.1111","volume":"181","author":[{"given":"Jacob A.","family":"Kinsella","sequence":"first","affiliation":[{"name":"Leeds Institute of Cardiovascular and Metabolic Medicine, School of Medicine University of Leeds  Leeds UK"},{"name":"School of Chemistry University of Leeds  Leeds UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolaine","family":"Debant","sequence":"additional","affiliation":[{"name":"Leeds Institute of Cardiovascular and Metabolic Medicine, 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