A novel adamantyl benzylbenzamide derivative, AP736, suppresses melanogenesis through the inhibition of cAMP-PKA-CREB-activated microphthalmia-associated transcription factor and tyrosinase expression
Melanogenesis is essential for the protection of skin against UV, but excessive production of melanin causes unaesthetic hyperpigmentation. Much effort is being made to develop effective depigmenting agents. Here, we found that a tyrosinase inhibitor, AP736 (5‐adamantan‐1‐yl‐N‐(2,4‐dihydroxy‐benzyl)...
Gespeichert in:
| Veröffentlicht in: | Experimental dermatology 2013-11, Vol.22 (11), p.762-764 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 764 |
|---|---|
| container_issue | 11 |
| container_start_page | 762 |
| container_title | Experimental dermatology |
| container_volume | 22 |
| creator | Lee, Chang Seok Jang, Won-Hee Park, Miyoung Jung, Kyoungmi Baek, Heung Soo Joo, Yung Hyup Park, Young-Ho Lim, Kyung-Min |
| description | Melanogenesis is essential for the protection of skin against UV, but excessive production of melanin causes unaesthetic hyperpigmentation. Much effort is being made to develop effective depigmenting agents. Here, we found that a tyrosinase inhibitor, AP736 (5‐adamantan‐1‐yl‐N‐(2,4‐dihydroxy‐benzyl)‐2,4‐dimethoxy‐benzamide) potently suppresses tyrosinase expression, and the mechanism underlying was elucidated. AP736 attenuated the melanin production induced by diverse melanogenic stimuli in murine and human melanocytes. It suppressed the expression of key melanogenic enzymes; tyrosinase, tyrosinase‐related protein‐1 and tyrosinase‐related protein‐2. The expression of microphthalmia‐associated transcription factor (MiTF), a major promoter of melanogenesis was also decreased. AP736 inhibited the activation of cAMP response element‐binding protein (CREB) and phosphokinase A (PKA), and cAMP elevation, reflecting that cAMP‐PKA‐CREB signalling axis was suppressed, resulting in the downregulation of MiTF and tyrosinase. Along with the previously reported tyrosinase inhibitory activity, the suppression of cAMP‐PKA‐CREB‐mediated MiTF and tyrosinase expression by AP736 may be efficient for the treatment for hyperpigmentation. |
| doi_str_mv | 10.1111/exd.12248 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1490722276</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1490722276</sourcerecordid><originalsourceid>FETCH-LOGICAL-i3248-d5095f8ae95cc7d7a743fa0a4458cb14e423e878b93d376301eb0044b36009683</originalsourceid><addsrcrecordid>eNo9Uctu1DAUtRCIDgMLfgB5yaJp7diJk2WYTltEgQHxmJ3lJDeNIYmDnQyTfmE_C0-m9C7utXQess5B6DUlZ9TPOezLMxqGPHmCFjQmJCBxGD1FC5KSOIgFiU7QC-d-EUIFE9FzdBJySgRJxQLdZ7gzO2iwKlWrumFqcA7d3dQctmp1CbgEq3dq0Ds4xdlGsPgUu7HvLTgHDrfQqM7cQgdOOzzU1oy3tb-AdVfrXA_adNhUuMg-boLNhyxYfV2_C1QxHDyhxK0urOnroVZNq1WgnDOFnpHBqs4VVvezReUlxmLVeWCyxulOOcCwn__hCS_Rs0o1Dl493CX6frn-troObj5fvV9lN4FmPqCgjEgaVYmCNCoKUQolOKsUUZxHSZFTDjxkkIgkT1nJRMwIhZwQznPmc03jhC3R26Nvb82fEdwgW-0KaHwKYEYnKU-JCMPQa5fozQN1zFsoZW91q-wk_6fvCedHwl_dwPSIUyIPtUpfq5xrlevtxfzwiuCo0G6A_aNC2d8yPnQrf366ktc_vmy3lzGVG_YPTuyoCw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1490722276</pqid></control><display><type>article</type><title>A novel adamantyl benzylbenzamide derivative, AP736, suppresses melanogenesis through the inhibition of cAMP-PKA-CREB-activated microphthalmia-associated transcription factor and tyrosinase expression</title><source>Wiley Online Library - AutoHoldings Journals</source><source>MEDLINE</source><creator>Lee, Chang Seok ; Jang, Won-Hee ; Park, Miyoung ; Jung, Kyoungmi ; Baek, Heung Soo ; Joo, Yung Hyup ; Park, Young-Ho ; Lim, Kyung-Min</creator><creatorcontrib>Lee, Chang Seok ; Jang, Won-Hee ; Park, Miyoung ; Jung, Kyoungmi ; Baek, Heung Soo ; Joo, Yung Hyup ; Park, Young-Ho ; Lim, Kyung-Min</creatorcontrib><description>Melanogenesis is essential for the protection of skin against UV, but excessive production of melanin causes unaesthetic hyperpigmentation. Much effort is being made to develop effective depigmenting agents. Here, we found that a tyrosinase inhibitor, AP736 (5‐adamantan‐1‐yl‐N‐(2,4‐dihydroxy‐benzyl)‐2,4‐dimethoxy‐benzamide) potently suppresses tyrosinase expression, and the mechanism underlying was elucidated. AP736 attenuated the melanin production induced by diverse melanogenic stimuli in murine and human melanocytes. It suppressed the expression of key melanogenic enzymes; tyrosinase, tyrosinase‐related protein‐1 and tyrosinase‐related protein‐2. The expression of microphthalmia‐associated transcription factor (MiTF), a major promoter of melanogenesis was also decreased. AP736 inhibited the activation of cAMP response element‐binding protein (CREB) and phosphokinase A (PKA), and cAMP elevation, reflecting that cAMP‐PKA‐CREB signalling axis was suppressed, resulting in the downregulation of MiTF and tyrosinase. Along with the previously reported tyrosinase inhibitory activity, the suppression of cAMP‐PKA‐CREB‐mediated MiTF and tyrosinase expression by AP736 may be efficient for the treatment for hyperpigmentation.</description><identifier>ISSN: 0906-6705</identifier><identifier>EISSN: 1600-0625</identifier><identifier>DOI: 10.1111/exd.12248</identifier><identifier>PMID: 24107097</identifier><language>eng</language><publisher>Denmark: Blackwell Publishing Ltd</publisher><subject>Adamantane - analogs & derivatives ; Adamantane - chemistry ; Animals ; Benzamides - chemistry ; cAMP response element-binding protein ; Cell Line, Tumor ; Cyclic AMP - metabolism ; Cyclic AMP Response Element-Binding Protein - metabolism ; Cyclic AMP-Dependent Protein Kinases - metabolism ; Gene Expression Regulation ; Humans ; Hyperpigmentation - metabolism ; Melanins - chemistry ; melanocyte ; Melanocytes - cytology ; melanogenesis ; Melanoma, Experimental - metabolism ; Mice ; microphthalmia-associated transcription factor ; Microphthalmia-Associated Transcription Factor - antagonists & inhibitors ; Monophenol Monooxygenase - antagonists & inhibitors ; Signal Transduction ; Skin - pathology ; Skin Neoplasms - metabolism ; tyrosinase</subject><ispartof>Experimental dermatology, 2013-11, Vol.22 (11), p.762-764</ispartof><rights>2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fexd.12248$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fexd.12248$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24107097$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Chang Seok</creatorcontrib><creatorcontrib>Jang, Won-Hee</creatorcontrib><creatorcontrib>Park, Miyoung</creatorcontrib><creatorcontrib>Jung, Kyoungmi</creatorcontrib><creatorcontrib>Baek, Heung Soo</creatorcontrib><creatorcontrib>Joo, Yung Hyup</creatorcontrib><creatorcontrib>Park, Young-Ho</creatorcontrib><creatorcontrib>Lim, Kyung-Min</creatorcontrib><title>A novel adamantyl benzylbenzamide derivative, AP736, suppresses melanogenesis through the inhibition of cAMP-PKA-CREB-activated microphthalmia-associated transcription factor and tyrosinase expression</title><title>Experimental dermatology</title><addtitle>Exp Dermatol</addtitle><description>Melanogenesis is essential for the protection of skin against UV, but excessive production of melanin causes unaesthetic hyperpigmentation. Much effort is being made to develop effective depigmenting agents. Here, we found that a tyrosinase inhibitor, AP736 (5‐adamantan‐1‐yl‐N‐(2,4‐dihydroxy‐benzyl)‐2,4‐dimethoxy‐benzamide) potently suppresses tyrosinase expression, and the mechanism underlying was elucidated. AP736 attenuated the melanin production induced by diverse melanogenic stimuli in murine and human melanocytes. It suppressed the expression of key melanogenic enzymes; tyrosinase, tyrosinase‐related protein‐1 and tyrosinase‐related protein‐2. The expression of microphthalmia‐associated transcription factor (MiTF), a major promoter of melanogenesis was also decreased. AP736 inhibited the activation of cAMP response element‐binding protein (CREB) and phosphokinase A (PKA), and cAMP elevation, reflecting that cAMP‐PKA‐CREB signalling axis was suppressed, resulting in the downregulation of MiTF and tyrosinase. Along with the previously reported tyrosinase inhibitory activity, the suppression of cAMP‐PKA‐CREB‐mediated MiTF and tyrosinase expression by AP736 may be efficient for the treatment for hyperpigmentation.</description><subject>Adamantane - analogs & derivatives</subject><subject>Adamantane - chemistry</subject><subject>Animals</subject><subject>Benzamides - chemistry</subject><subject>cAMP response element-binding protein</subject><subject>Cell Line, Tumor</subject><subject>Cyclic AMP - metabolism</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Hyperpigmentation - metabolism</subject><subject>Melanins - chemistry</subject><subject>melanocyte</subject><subject>Melanocytes - cytology</subject><subject>melanogenesis</subject><subject>Melanoma, Experimental - metabolism</subject><subject>Mice</subject><subject>microphthalmia-associated transcription factor</subject><subject>Microphthalmia-Associated Transcription Factor - antagonists & inhibitors</subject><subject>Monophenol Monooxygenase - antagonists & inhibitors</subject><subject>Signal Transduction</subject><subject>Skin - pathology</subject><subject>Skin Neoplasms - metabolism</subject><subject>tyrosinase</subject><issn>0906-6705</issn><issn>1600-0625</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9Uctu1DAUtRCIDgMLfgB5yaJp7diJk2WYTltEgQHxmJ3lJDeNIYmDnQyTfmE_C0-m9C7utXQess5B6DUlZ9TPOezLMxqGPHmCFjQmJCBxGD1FC5KSOIgFiU7QC-d-EUIFE9FzdBJySgRJxQLdZ7gzO2iwKlWrumFqcA7d3dQctmp1CbgEq3dq0Ds4xdlGsPgUu7HvLTgHDrfQqM7cQgdOOzzU1oy3tb-AdVfrXA_adNhUuMg-boLNhyxYfV2_C1QxHDyhxK0urOnroVZNq1WgnDOFnpHBqs4VVvezReUlxmLVeWCyxulOOcCwn__hCS_Rs0o1Dl493CX6frn-troObj5fvV9lN4FmPqCgjEgaVYmCNCoKUQolOKsUUZxHSZFTDjxkkIgkT1nJRMwIhZwQznPmc03jhC3R26Nvb82fEdwgW-0KaHwKYEYnKU-JCMPQa5fozQN1zFsoZW91q-wk_6fvCedHwl_dwPSIUyIPtUpfq5xrlevtxfzwiuCo0G6A_aNC2d8yPnQrf366ktc_vmy3lzGVG_YPTuyoCw</recordid><startdate>201311</startdate><enddate>201311</enddate><creator>Lee, Chang Seok</creator><creator>Jang, Won-Hee</creator><creator>Park, Miyoung</creator><creator>Jung, Kyoungmi</creator><creator>Baek, Heung Soo</creator><creator>Joo, Yung Hyup</creator><creator>Park, Young-Ho</creator><creator>Lim, Kyung-Min</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201311</creationdate><title>A novel adamantyl benzylbenzamide derivative, AP736, suppresses melanogenesis through the inhibition of cAMP-PKA-CREB-activated microphthalmia-associated transcription factor and tyrosinase expression</title><author>Lee, Chang Seok ; Jang, Won-Hee ; Park, Miyoung ; Jung, Kyoungmi ; Baek, Heung Soo ; Joo, Yung Hyup ; Park, Young-Ho ; Lim, Kyung-Min</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i3248-d5095f8ae95cc7d7a743fa0a4458cb14e423e878b93d376301eb0044b36009683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adamantane - analogs & derivatives</topic><topic>Adamantane - chemistry</topic><topic>Animals</topic><topic>Benzamides - chemistry</topic><topic>cAMP response element-binding protein</topic><topic>Cell Line, Tumor</topic><topic>Cyclic AMP - metabolism</topic><topic>Cyclic AMP Response Element-Binding Protein - metabolism</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Hyperpigmentation - metabolism</topic><topic>Melanins - chemistry</topic><topic>melanocyte</topic><topic>Melanocytes - cytology</topic><topic>melanogenesis</topic><topic>Melanoma, Experimental - metabolism</topic><topic>Mice</topic><topic>microphthalmia-associated transcription factor</topic><topic>Microphthalmia-Associated Transcription Factor - antagonists & inhibitors</topic><topic>Monophenol Monooxygenase - antagonists & inhibitors</topic><topic>Signal Transduction</topic><topic>Skin - pathology</topic><topic>Skin Neoplasms - metabolism</topic><topic>tyrosinase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Chang Seok</creatorcontrib><creatorcontrib>Jang, Won-Hee</creatorcontrib><creatorcontrib>Park, Miyoung</creatorcontrib><creatorcontrib>Jung, Kyoungmi</creatorcontrib><creatorcontrib>Baek, Heung Soo</creatorcontrib><creatorcontrib>Joo, Yung Hyup</creatorcontrib><creatorcontrib>Park, Young-Ho</creatorcontrib><creatorcontrib>Lim, Kyung-Min</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental dermatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Chang Seok</au><au>Jang, Won-Hee</au><au>Park, Miyoung</au><au>Jung, Kyoungmi</au><au>Baek, Heung Soo</au><au>Joo, Yung Hyup</au><au>Park, Young-Ho</au><au>Lim, Kyung-Min</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel adamantyl benzylbenzamide derivative, AP736, suppresses melanogenesis through the inhibition of cAMP-PKA-CREB-activated microphthalmia-associated transcription factor and tyrosinase expression</atitle><jtitle>Experimental dermatology</jtitle><addtitle>Exp Dermatol</addtitle><date>2013-11</date><risdate>2013</risdate><volume>22</volume><issue>11</issue><spage>762</spage><epage>764</epage><pages>762-764</pages><issn>0906-6705</issn><eissn>1600-0625</eissn><abstract>Melanogenesis is essential for the protection of skin against UV, but excessive production of melanin causes unaesthetic hyperpigmentation. Much effort is being made to develop effective depigmenting agents. Here, we found that a tyrosinase inhibitor, AP736 (5‐adamantan‐1‐yl‐N‐(2,4‐dihydroxy‐benzyl)‐2,4‐dimethoxy‐benzamide) potently suppresses tyrosinase expression, and the mechanism underlying was elucidated. AP736 attenuated the melanin production induced by diverse melanogenic stimuli in murine and human melanocytes. It suppressed the expression of key melanogenic enzymes; tyrosinase, tyrosinase‐related protein‐1 and tyrosinase‐related protein‐2. The expression of microphthalmia‐associated transcription factor (MiTF), a major promoter of melanogenesis was also decreased. AP736 inhibited the activation of cAMP response element‐binding protein (CREB) and phosphokinase A (PKA), and cAMP elevation, reflecting that cAMP‐PKA‐CREB signalling axis was suppressed, resulting in the downregulation of MiTF and tyrosinase. Along with the previously reported tyrosinase inhibitory activity, the suppression of cAMP‐PKA‐CREB‐mediated MiTF and tyrosinase expression by AP736 may be efficient for the treatment for hyperpigmentation.</abstract><cop>Denmark</cop><pub>Blackwell Publishing Ltd</pub><pmid>24107097</pmid><doi>10.1111/exd.12248</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0906-6705 |
| ispartof | Experimental dermatology, 2013-11, Vol.22 (11), p.762-764 |
| issn | 0906-6705 1600-0625 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1490722276 |
| source | Wiley Online Library - AutoHoldings Journals; MEDLINE |
| subjects | Adamantane - analogs & derivatives Adamantane - chemistry Animals Benzamides - chemistry cAMP response element-binding protein Cell Line, Tumor Cyclic AMP - metabolism Cyclic AMP Response Element-Binding Protein - metabolism Cyclic AMP-Dependent Protein Kinases - metabolism Gene Expression Regulation Humans Hyperpigmentation - metabolism Melanins - chemistry melanocyte Melanocytes - cytology melanogenesis Melanoma, Experimental - metabolism Mice microphthalmia-associated transcription factor Microphthalmia-Associated Transcription Factor - antagonists & inhibitors Monophenol Monooxygenase - antagonists & inhibitors Signal Transduction Skin - pathology Skin Neoplasms - metabolism tyrosinase |
| title | A novel adamantyl benzylbenzamide derivative, AP736, suppresses melanogenesis through the inhibition of cAMP-PKA-CREB-activated microphthalmia-associated transcription factor and tyrosinase expression |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-03T10%3A06%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20novel%20adamantyl%20benzylbenzamide%20derivative,%20AP736,%20suppresses%20melanogenesis%20through%20the%20inhibition%20of%20cAMP-PKA-CREB-activated%20microphthalmia-associated%20transcription%20factor%20and%20tyrosinase%20expression&rft.jtitle=Experimental%20dermatology&rft.au=Lee,%20Chang%20Seok&rft.date=2013-11&rft.volume=22&rft.issue=11&rft.spage=762&rft.epage=764&rft.pages=762-764&rft.issn=0906-6705&rft.eissn=1600-0625&rft_id=info:doi/10.1111/exd.12248&rft_dat=%3Cproquest_pubme%3E1490722276%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1490722276&rft_id=info:pmid/24107097&rfr_iscdi=true |