{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T17:24:59Z","timestamp":1763745899625,"version":"3.45.0"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cosmetic Dermatology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tyrosinase is the rate\u2010limiting enzyme in melanin biosynthesis, and its overactivity contributes to hyperpigmentation disorders. Existing tyrosinase inhibitors are often limited by poor potency against human tyrosinase (hTYR) or safety concerns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To evaluate the inhibitory potency, safety, and multifunctional activity of KT\u2010939, a newly synthesized human tyrosinase inhibitor, compared with established depigmenting agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients\/Methods<\/jats:title>\n                    <jats:p>KT\u2010939 was synthesized and tested in\u00a0vitro for tyrosinase inhibition, melanin suppression in human melanocytes, antioxidant activity (DPPH radical scavenging, NRF2 pathway activation), and anti\u2010inflammatory activity (cytokine expression in LPS\u2010stimulated macrophages). Safety was assessed in multiple skin\u2010related cell lines. A 28\u2010day, single\u2010center clinical study in healthy women with sensitive skin assessed the effects of 0.2% KT\u2010939 lotion on pigmentation and tolerability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>KT\u2010939 strongly inhibited hTYR (IC\u2085\u2080\u2009=\u20090.07\u2009\u03bcM), demonstrating ~4\u2010fold greater potency than Thiamidol and far surpassing other comparators. In melanocytes, KT\u2010939 reduced melanin production (IC\u2085\u2080\u2009=\u20090.36\u2009\u03bcM) with reversible effects upon withdrawal. KT\u2010939 also displayed antioxidant activity, NRF2 activation, and suppression of pro\u2010inflammatory cytokines, without cytotoxicity up to 50\u2009\u03bcM. Clinically, 28\u2009days of KT\u2010939 lotion use improved skin spot lightening, tone uniformity, and overall brightness, with good tolerability in sensitive skin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>KT\u2010939 is a potent and safe human tyrosinase inhibitor with additional antioxidant and anti\u2010inflammatory activity. These findings support its potential in cosmetic skin brightening and as a therapeutic candidate for hyperpigmentation disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jocd.70510","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T18:20:02Z","timestamp":1761762002000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>KT<\/scp>\n                    \u2010939: A Next\u2010Generation Human Tyrosinase Inhibitor With Superior Efficacy for the Safe Management of Hyperpigmentation"],"prefix":"10.1111","volume":"24","author":[{"given":"Xiaodan","family":"Hou","sequence":"first","affiliation":[{"name":"Kintor Pharmaceutical Limited  Suzhou Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunhui","family":"Li","sequence":"additional","affiliation":[{"name":"Kintor Pharmaceutical Limited  Suzhou Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Kintor Pharmaceutical Limited  Suzhou Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honghua","family":"Yan","sequence":"additional","affiliation":[{"name":"Kintor Pharmaceutical Limited  Suzhou Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Kintor Pharmaceutical Limited  Suzhou Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueying","family":"Yang","sequence":"additional","affiliation":[{"name":"Kintor Pharmaceutical Limited  Suzhou Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Cai","sequence":"additional","affiliation":[{"name":"Kintor Pharmaceutical Limited  Suzhou Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Wang","sequence":"additional","affiliation":[{"name":"Kintor Pharmaceutical Limited  Suzhou Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miaohua","family":"Ding","sequence":"additional","affiliation":[{"name":"Kintor Pharmaceutical Limited  Suzhou Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Chen","sequence":"additional","affiliation":[{"name":"Kintor Pharmaceutical Limited  Suzhou Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Kintor Pharmaceutical Limited  Suzhou Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youzhi","family":"Tong","sequence":"additional","affiliation":[{"name":"Kintor Pharmaceutical Limited  Suzhou Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7745-9993","authenticated-orcid":false,"given":"Nina","family":"Mehta","sequence":"additional","affiliation":[{"name":"The University of North Carolina School of Medicine  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andy","family":"Goren","sequence":"additional","affiliation":[{"name":"University of Rome \u201cG. 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