{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T19:03:03Z","timestamp":1780599783309,"version":"3.54.1"},"posted":{"date-parts":[[2025,10,15]]},"group-title":"Pharmacology and Toxicology","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"DOI":"10.13039\/100000069","name":"NIAMS","doi-asserted-by":"crossref","award":["1 R01 AR077664-01A1"],"award-info":[{"award-number":["1 R01 AR077664-01A1"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NCI","award":["T32 CA062948"],"award-info":[{"award-number":["T32 CA062948"]}]},{"name":"National Organization for Albinism and Hypopigmentation"},{"name":"Intramural Research Program of the National Institutes of Health"},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Significant loss of pigmentation can increase visual disability, skin cancer risk, and psychosocial stress. Tyrosinase (TYR) catalyzes the first and rate-limiting step of melanin synthesis. Inhibitors of TYR are well established and are currently used in clinical settings; however, there is a dearth of direct activators of TYR. Here, using a unique human TYR construct, high-throughput screening, and computational analysis techniques, we identified ampyrone as a TYR activator. Ampyrone increased the\n                  <jats:italic>in vitro<\/jats:italic>\n                  catalytic activity of the intramelanosomal domain of human TYR (hTYR) and its hypomorphic variant, P406L, a cause of oculocutaneous albinism type 1B (OCA1B). Moreover, ampyrone induced melanin synthesis in both wild-type and OCA1B human melanocytes, as well as 3-dimension (3D) human skin cultures. Our results reveal ampyrone as a lead compound for first-in-class TYR activators, potentially accelerating the discovery of novel therapies for patients with genetic and acquired diseases of hypopigmentation.\n                <\/jats:p>","DOI":"10.1101\/2025.10.13.682036","type":"posted-content","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T20:20:13Z","timestamp":1760559613000},"source":"Crossref","is-referenced-by-count":1,"title":["Ampyrone (4-Aminoantipyrine) is a Direct Agonist of Human Tyrosinase and Potential Therapeutic for Oculocutaneous Albinism and Disorders of Hypopigmentation"],"prefix":"10.64898","author":[{"given":"Monika B.","family":"Dolinska","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan P.","family":"Coussens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay K.","family":"Kalaskar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuhal","family":"Eraslan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel J.","family":"Grondin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Bonica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Toay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Boxer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5909-3959","authenticated-orcid":false,"given":"Qiuying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven S","family":"Gross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabeel","family":"Attarwala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyos","family":"Jittayasothorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramakrishna P.","family":"Alur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhyanam","family":"Shukla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Kee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"DeYoung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuilee","family":"Sha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacie","family":"Loftus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Cogliati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri V.","family":"Sergeev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan H.","family":"Zippin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P.","family":"Brooks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025101705450549000_2025.10.13.682036v1.1","unstructured":"M. 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