Identification of A Novel Small-Molecule Binding Site of the Fat Mass and Obesity Associated Protein (FTO)
N-(5-Chloro-2,4-dihydroxyphenyl)-1-phenylcyclobutanecarboxamide (N-CDPCB, 1a) is found to be an inhibitor of the fat mass and obesity associated protein (FTO). The crystal structure of human FTO with 1a reveals a novel binding site for the FTO inhibitor and defines the molecular basis for recognitio...
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| Veröffentlicht in: | Journal of medicinal chemistry 2015-09, Vol.58 (18), p.7341-7348 |
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| container_title | Journal of medicinal chemistry |
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| creator | He, Wu Zhou, Bin Liu, Weijia Zhang, Meizi Shen, Zhenhua Han, Zhifu Jiang, Qingwei Yang, Qinghua Song, Chuanjun Wang, Ruiyong Niu, Tianhui Han, Shengna Zhang, Lirong Wu, Jie Guo, Feima Zhao, Renbin Yu, Wenquan Chai, Jijie Chang, Junbiao |
| description | N-(5-Chloro-2,4-dihydroxyphenyl)-1-phenylcyclobutanecarboxamide (N-CDPCB, 1a) is found to be an inhibitor of the fat mass and obesity associated protein (FTO). The crystal structure of human FTO with 1a reveals a novel binding site for the FTO inhibitor and defines the molecular basis for recognition by FTO of the inhibitor. The identification of the new binding site offers new opportunities for further development of selective and potent inhibitors of FTO, which is expected to provide information concerning novel therapeutic targets for treatment of obesity or obesity-associated diseases. |
| doi_str_mv | 10.1021/acs.jmedchem.5b00702 |
| format | Article |
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The crystal structure of human FTO with 1a reveals a novel binding site for the FTO inhibitor and defines the molecular basis for recognition by FTO of the inhibitor. The identification of the new binding site offers new opportunities for further development of selective and potent inhibitors of FTO, which is expected to provide information concerning novel therapeutic targets for treatment of obesity or obesity-associated diseases.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/acs.jmedchem.5b00702</identifier><identifier>PMID: 26314339</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>3T3-L1 Cells ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO ; Aminophenols - chemical synthesis ; Aminophenols - chemistry ; Aminophenols - pharmacology ; Anilides - chemical synthesis ; Anilides - chemistry ; Anilides - pharmacology ; Animals ; Binding Sites ; Crystallography, X-Ray ; Databases, Chemical ; Humans ; Methylation ; Mice ; Models, Molecular ; Protein Binding ; Proteins - antagonists & inhibitors ; Proteins - chemistry ; RNA - chemistry ; RNA, Messenger - metabolism</subject><ispartof>Journal of medicinal chemistry, 2015-09, Vol.58 (18), p.7341-7348</ispartof><rights>Copyright © 2015 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a414t-7fc7d8c8f99fbb1c92e1a4af886ee9ee64cf700b027218663fc6096c3599a8453</citedby><cites>FETCH-LOGICAL-a414t-7fc7d8c8f99fbb1c92e1a4af886ee9ee64cf700b027218663fc6096c3599a8453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.5b00702$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.jmedchem.5b00702$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26314339$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>He, Wu</creatorcontrib><creatorcontrib>Zhou, Bin</creatorcontrib><creatorcontrib>Liu, Weijia</creatorcontrib><creatorcontrib>Zhang, Meizi</creatorcontrib><creatorcontrib>Shen, Zhenhua</creatorcontrib><creatorcontrib>Han, Zhifu</creatorcontrib><creatorcontrib>Jiang, Qingwei</creatorcontrib><creatorcontrib>Yang, Qinghua</creatorcontrib><creatorcontrib>Song, Chuanjun</creatorcontrib><creatorcontrib>Wang, Ruiyong</creatorcontrib><creatorcontrib>Niu, Tianhui</creatorcontrib><creatorcontrib>Han, Shengna</creatorcontrib><creatorcontrib>Zhang, Lirong</creatorcontrib><creatorcontrib>Wu, Jie</creatorcontrib><creatorcontrib>Guo, Feima</creatorcontrib><creatorcontrib>Zhao, Renbin</creatorcontrib><creatorcontrib>Yu, Wenquan</creatorcontrib><creatorcontrib>Chai, Jijie</creatorcontrib><creatorcontrib>Chang, Junbiao</creatorcontrib><title>Identification of A Novel Small-Molecule Binding Site of the Fat Mass and Obesity Associated Protein (FTO)</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>N-(5-Chloro-2,4-dihydroxyphenyl)-1-phenylcyclobutanecarboxamide (N-CDPCB, 1a) is found to be an inhibitor of the fat mass and obesity associated protein (FTO). The crystal structure of human FTO with 1a reveals a novel binding site for the FTO inhibitor and defines the molecular basis for recognition by FTO of the inhibitor. The identification of the new binding site offers new opportunities for further development of selective and potent inhibitors of FTO, which is expected to provide information concerning novel therapeutic targets for treatment of obesity or obesity-associated diseases.</description><subject>3T3-L1 Cells</subject><subject>Alpha-Ketoglutarate-Dependent Dioxygenase FTO</subject><subject>Aminophenols - chemical synthesis</subject><subject>Aminophenols - chemistry</subject><subject>Aminophenols - pharmacology</subject><subject>Anilides - chemical synthesis</subject><subject>Anilides - chemistry</subject><subject>Anilides - pharmacology</subject><subject>Animals</subject><subject>Binding Sites</subject><subject>Crystallography, X-Ray</subject><subject>Databases, Chemical</subject><subject>Humans</subject><subject>Methylation</subject><subject>Mice</subject><subject>Models, Molecular</subject><subject>Protein Binding</subject><subject>Proteins - antagonists & inhibitors</subject><subject>Proteins - chemistry</subject><subject>RNA - chemistry</subject><subject>RNA, Messenger - metabolism</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1P20AQhleoiITQf1BVe6QHh9kPr73HFDUtEhAk6Nlar2fLRraXetdI-fd1SOiR0xzmed_RPIR8YbBkwNmVsXG57bCxz9gt8xqgAH5C5iznkMkS5CcyB-A844qLGTmPcQsAgnFxRmZcCSaF0HOyvWmwT955a5IPPQ2Oruh9eMWWPnambbO70KIdW6Tffd_4_g999An3WHpGujaJ3pkYqekbuqkx-rSjqxiD9SZhQx-GkND39HL9tPl2QU6daSN-Ps4F-b3-8XT9K7vd_Ly5Xt1mRjKZssLZoilt6bR2dc2s5siMNK4sFaJGVNK6AqAGXnBWKiWcVaCVFbnWppS5WJDLQ-_LEP6OGFPV-WixbU2PYYwVK5jSoihzOaHygNohxDigq14G35lhVzGo9paryXL1brk6Wp5iX48Xxnra_Q-9a50AOABv8TAO_fTwx53_AMyAiwg</recordid><startdate>20150924</startdate><enddate>20150924</enddate><creator>He, Wu</creator><creator>Zhou, Bin</creator><creator>Liu, Weijia</creator><creator>Zhang, Meizi</creator><creator>Shen, Zhenhua</creator><creator>Han, Zhifu</creator><creator>Jiang, Qingwei</creator><creator>Yang, Qinghua</creator><creator>Song, Chuanjun</creator><creator>Wang, Ruiyong</creator><creator>Niu, Tianhui</creator><creator>Han, Shengna</creator><creator>Zhang, Lirong</creator><creator>Wu, Jie</creator><creator>Guo, Feima</creator><creator>Zhao, Renbin</creator><creator>Yu, Wenquan</creator><creator>Chai, Jijie</creator><creator>Chang, Junbiao</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20150924</creationdate><title>Identification of A Novel Small-Molecule Binding Site of the Fat Mass and Obesity Associated Protein (FTO)</title><author>He, Wu ; Zhou, Bin ; Liu, Weijia ; Zhang, Meizi ; Shen, Zhenhua ; Han, Zhifu ; Jiang, Qingwei ; Yang, Qinghua ; Song, Chuanjun ; Wang, Ruiyong ; Niu, Tianhui ; Han, Shengna ; Zhang, Lirong ; Wu, Jie ; Guo, Feima ; Zhao, Renbin ; Yu, Wenquan ; Chai, Jijie ; Chang, Junbiao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a414t-7fc7d8c8f99fbb1c92e1a4af886ee9ee64cf700b027218663fc6096c3599a8453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>3T3-L1 Cells</topic><topic>Alpha-Ketoglutarate-Dependent Dioxygenase FTO</topic><topic>Aminophenols - chemical synthesis</topic><topic>Aminophenols - chemistry</topic><topic>Aminophenols - pharmacology</topic><topic>Anilides - chemical synthesis</topic><topic>Anilides - chemistry</topic><topic>Anilides - pharmacology</topic><topic>Animals</topic><topic>Binding Sites</topic><topic>Crystallography, X-Ray</topic><topic>Databases, Chemical</topic><topic>Humans</topic><topic>Methylation</topic><topic>Mice</topic><topic>Models, Molecular</topic><topic>Protein Binding</topic><topic>Proteins - antagonists & inhibitors</topic><topic>Proteins - chemistry</topic><topic>RNA - chemistry</topic><topic>RNA, Messenger - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>He, Wu</creatorcontrib><creatorcontrib>Zhou, Bin</creatorcontrib><creatorcontrib>Liu, Weijia</creatorcontrib><creatorcontrib>Zhang, Meizi</creatorcontrib><creatorcontrib>Shen, Zhenhua</creatorcontrib><creatorcontrib>Han, Zhifu</creatorcontrib><creatorcontrib>Jiang, Qingwei</creatorcontrib><creatorcontrib>Yang, Qinghua</creatorcontrib><creatorcontrib>Song, Chuanjun</creatorcontrib><creatorcontrib>Wang, Ruiyong</creatorcontrib><creatorcontrib>Niu, Tianhui</creatorcontrib><creatorcontrib>Han, Shengna</creatorcontrib><creatorcontrib>Zhang, Lirong</creatorcontrib><creatorcontrib>Wu, Jie</creatorcontrib><creatorcontrib>Guo, Feima</creatorcontrib><creatorcontrib>Zhao, Renbin</creatorcontrib><creatorcontrib>Yu, Wenquan</creatorcontrib><creatorcontrib>Chai, Jijie</creatorcontrib><creatorcontrib>Chang, Junbiao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>He, Wu</au><au>Zhou, Bin</au><au>Liu, Weijia</au><au>Zhang, Meizi</au><au>Shen, Zhenhua</au><au>Han, Zhifu</au><au>Jiang, Qingwei</au><au>Yang, Qinghua</au><au>Song, Chuanjun</au><au>Wang, Ruiyong</au><au>Niu, Tianhui</au><au>Han, Shengna</au><au>Zhang, Lirong</au><au>Wu, Jie</au><au>Guo, Feima</au><au>Zhao, Renbin</au><au>Yu, Wenquan</au><au>Chai, Jijie</au><au>Chang, Junbiao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of A Novel Small-Molecule Binding Site of the Fat Mass and Obesity Associated Protein (FTO)</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2015-09-24</date><risdate>2015</risdate><volume>58</volume><issue>18</issue><spage>7341</spage><epage>7348</epage><pages>7341-7348</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>N-(5-Chloro-2,4-dihydroxyphenyl)-1-phenylcyclobutanecarboxamide (N-CDPCB, 1a) is found to be an inhibitor of the fat mass and obesity associated protein (FTO). The crystal structure of human FTO with 1a reveals a novel binding site for the FTO inhibitor and defines the molecular basis for recognition by FTO of the inhibitor. The identification of the new binding site offers new opportunities for further development of selective and potent inhibitors of FTO, which is expected to provide information concerning novel therapeutic targets for treatment of obesity or obesity-associated diseases.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>26314339</pmid><doi>10.1021/acs.jmedchem.5b00702</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 2015-09, Vol.58 (18), p.7341-7348 |
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| source | ACS Publications; MEDLINE |
| subjects | 3T3-L1 Cells Alpha-Ketoglutarate-Dependent Dioxygenase FTO Aminophenols - chemical synthesis Aminophenols - chemistry Aminophenols - pharmacology Anilides - chemical synthesis Anilides - chemistry Anilides - pharmacology Animals Binding Sites Crystallography, X-Ray Databases, Chemical Humans Methylation Mice Models, Molecular Protein Binding Proteins - antagonists & inhibitors Proteins - chemistry RNA - chemistry RNA, Messenger - metabolism |
| title | Identification of A Novel Small-Molecule Binding Site of the Fat Mass and Obesity Associated Protein (FTO) |
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