{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:25:43Z","timestamp":1791188743228,"version":"4.1.0"},"reference-count":9,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,3,9]],"date-time":"2015-03-09T00:00:00Z","timestamp":1425859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Azole antimycotic agents are known to have anti\u2010inflammatory and anti\u2010cancer effects, which are mediated through their effects on the p38\u2010cyclooxygenase\u20102 (<jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20102)\u2010prostaglandin E2 (<jats:styled-content style=\"fixed-case\">PGE<\/jats:styled-content>2) pathway, as well as anti\u2010oxidant effects. Furthermore, pyridinyl imidazole compounds, such as <jats:styled-content style=\"fixed-case\">SB<\/jats:styled-content>203580 have recently been shown to inhibit melanogenesis. Accordingly, we hypothesized that azole antifungal agents might affect skin pigmentation. We herein investigated the effect of clotrimazole, the most commonly used azole antifungal agent, on melanogenesis. Intriguingly, clotrimazole reduced the melanin content in human melanocytes and mouse melanocytes, as well as in B16F10 mouse melanoma cells. Clotrimazole reduced levels of tyrosinase protein without altering <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression. Simultaneous treatment with a proteasomal inhibitor restored both the suppression of melanin synthesis, and the downregulation of tyrosinase level, by clotrimazole. Clotrimazole also induced the phosphorylation of extracellular signal\u2010regulated kinase (<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\/Akt, while each inhibitor of these two signals abolished the decrease of melanin synthesis by clotrimazole. Thus, our data suggest that clotrimazole inhibits melanin synthesis by promoting the proteasomal degradation of tyrosinase, which is mediated through activation of the <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> and Akt signaling pathways. These results may indicate a new role for clotrimazole as a molecular\u2010mechanism\u2010based, safe depigmenting agent for topical management of hyper\u2010pigmentary sequelae related to fungal infection, or for other skin inflammatory disorders.<\/jats:p>","DOI":"10.1111\/exd.12669","type":"journal-article","created":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T05:41:13Z","timestamp":1424238073000},"page":"386-388","source":"Crossref","is-referenced-by-count":16,"title":["The antimycotic agent clotrimazole inhibits melanogenesis by accelerating <scp>ERK<\/scp> and <scp>PI<\/scp>3K\u2010\/Akt\u2010mediated tyrosinase degradation"],"prefix":"10.1111","volume":"24","author":[{"given":"Bo Young","family":"Chung","sequence":"first","affiliation":[{"name":"Department of Dermatology College of Medicine Hallym University Kangnam Sacred Heart Hospital Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology Asan Medical Center University of Ulsan College of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon Min","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Dermatology Asan Medical Center University of Ulsan College of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong Hyun","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Dermatology Asan Medical Center University of Ulsan College of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Asan Medical Center University of Ulsan College of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Woo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology Asan Medical Center University of Ulsan College of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Eun","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Dermatology Asan Medical Center University of Ulsan College of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,9]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5701157"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2011.194"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2007.04.046"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-148X.2010.00696.x"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096035"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033021"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.070573"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2012.01508.x"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12028"}],"container-title":["Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fexd.12669","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.12669","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T21:04:09Z","timestamp":1696280649000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/exd.12669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,9]]},"references-count":9,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1111\/exd.12669"],"URL":"https:\/\/doi.org\/10.1111\/exd.12669","archive":["Portico"],"relation":{},"ISSN":["0906-6705","1600-0625"],"issn-type":[{"value":"0906-6705","type":"print"},{"value":"1600-0625","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,9]]}}}