{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:21:45Z","timestamp":1787509305509,"version":"build-2736575974"},"reference-count":51,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":67,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["Intramural program"],"award-info":[{"award-number":["Intramural program"]}],"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","award":["Intramural program"],"award-info":[{"award-number":["Intramural program"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["1 RO1 AR077664-01A1"],"award-info":[{"award-number":["1 RO1 AR077664-01A1"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Organization for Albinism and Hypopigmentation","award":["Established Researcher Program Grant"],"award-info":[{"award-number":["Established Researcher Program Grant"]}]},{"name":"National Cancer Institute","award":["T32 CA062948"],"award-info":[{"award-number":["T32 CA062948"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,24]]},"abstract":"<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 human TYR construct, we developed high-throughput screening methods, in cell confirmatory assays employing\n                    <jats:sup>13<\/jats:sup>\n                    C-tyrosine tracing, and computational analysis techniques, and identified ampyrone (4-aminoantipyrine) as a TYR activator. Ampyrone increased the in vitro catalytic activity of the human recombinant intramelanosomal domain of TYR (hTYR) and its hypomorphic variant, Pro406Leu (P406L), a cause of oculocutaneous albinism type 1B (OCA1B). Moreover, ampyrone induced melanin synthesis in both WT and OCA1B human melanocytes, mouse OCA2 melanocytes, as well as 3-dimensional (3D) human skin cultures. Computational studies provided additional insight into the effects of direct TYR agonists on enzyme activity. Our results identify ampyrone as a lead candidate for TYR activation, potentially supporting the development of therapies for patients with genetic and acquired diseases of hypopigmentation.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.202947","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T16:00:19Z","timestamp":1781798419000},"source":"Crossref","is-referenced-by-count":0,"title":["Ampyrone is a direct agonist of human tyrosinase and a potential therapeutic for hypopigmentation disorders"],"prefix":"10.1172","volume":"11","author":[{"given":"Monika B.","family":"Dolinska","sequence":"first","affiliation":[{"name":"National Eye Institute, National Institutes of Health, Bethesda, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhong","family":"Wang","sequence":"additional","affiliation":[{"name":"National Eye Institute, National Institutes of Health, Bethesda, 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