{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:25:47Z","timestamp":1792686347467,"version":"4.5.0"},"reference-count":92,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,8,3]],"date-time":"2024-08-03T00:00:00Z","timestamp":1722643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nitric oxide (NO) has been defined as the \u201cmiracle molecule\u201d due to its essential pleiotropic role in living systems. Besides its implications in physiologic functions, it is also involved in the development of several disease states, and understanding this ambivalence is crucial for medicinal chemists to develop therapeutic strategies that regulate NO production without compromising its beneficial functions in cell physiology. Although nitric oxide synthase (NOS), i.e., the enzyme deputed to the NO biosynthesis, is a well-recognized druggable target to regulate NO bioavailability, some issues have emerged during the past decades, limiting the progress of NOS modulators in clinical trials. In the present review, we discuss the most promising advancements in the research of small molecules that are able to regulate NOS activity with improved pharmacodynamic and pharmacokinetic profiles, providing an updated framework of this research field that could be useful for the design and development of new NOS modulators.<\/jats:p>","DOI":"10.3390\/ijms25158486","type":"journal-article","created":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T15:45:22Z","timestamp":1722872722000},"page":"8486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Advancements in the Research of New Modulators of Nitric Oxide Synthases Activity"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2957-8650","authenticated-orcid":false,"given":"Cristina","family":"Maccallini","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8454-9740","authenticated-orcid":false,"given":"Roberta","family":"Budriesi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, Food Chemistry and Nutraceutical Lab, Alma Mater Studiorum-University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7718-5814","authenticated-orcid":false,"given":"Barbara","family":"De Filippis","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8282-8535","authenticated-orcid":false,"given":"Rosa","family":"Amoroso","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1038\/3182","article-title":"Nobel Prize for NO research","volume":"11","author":"Smith","year":"1998","journal-title":"Nat. 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