Design of potent and highly selective inhibitors for human β-secretase 2 (memapsin 1), a target for type 2 diabetes
Design, synthesis and evaluation of very potent and selective β-secretase 2 (memapsin 1, BACE 2) inhibitors are described. The inhibitors were designed specifically to interact with the S2′-site of β-secretase 2 to provide >170 000-fold selectivity over β-secretase (BACE 1) and >15 000-fold se...
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| Veröffentlicht in: | Chemical science (Cambridge) 2016-01, Vol.7 (5), p.3117-3122 |
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| container_title | Chemical science (Cambridge) |
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| creator | Ghosh, Arun K Reddy, Bhavanam Sekhara Yen, Yu-Chen Cárdenas, Emilio L Rao, Kalapala Venkateswara Downs, Deborah Huang, Xiangping Tang, Jordan Mesecar, Andrew D |
| description | Design, synthesis and evaluation of very potent and selective β-secretase 2 (memapsin 1, BACE 2) inhibitors are described. The inhibitors were designed specifically to interact with the S2′-site of β-secretase 2 to provide >170 000-fold selectivity over β-secretase (BACE 1) and >15 000-fold selectivity over cathepsin D. BACE 2 is implicated in type 2 diabetes. The studies serve as an important guide to selective BACE 2 inhibitors.
Structure-based design and syntheses of potent and highly selective BACE2 inhibitors are described. |
| doi_str_mv | 10.1039/c5sc03718b |
| format | Article |
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Structure-based design and syntheses of potent and highly selective BACE2 inhibitors are described.</description><subject>Cathepsin D</subject><subject>Design analysis</subject><subject>Diabetes</subject><subject>Human</subject><subject>Inhibitors</subject><subject>Selectivity</subject><subject>Synthesis</subject><issn>2041-6520</issn><issn>2041-6539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNqN0c9u1DAQBnALgWhVeuEOsjgVRMB_Ysc5loWWSpU4AOfIccYbo8QOHi_SvhYPwjN1t1uWK76Mpfnpk0YfIc85e8eZbN87hY7Jhpv-ETkVrOaVVrJ9fPwLdkLOEX-w3ZOSK9E8JSeikXUjtT4l5SNgWEeaPF1SgViojQMdw3qcthRhAlfCL6AhjqEPJWWkPmU6bmYb6Z_fFYLLUCwCFfRihtkuGCLlr99SS4vNayj3vmyXvRiC7aEAPiNPvJ0Qzh_mGfl-9enb6nN1--X6ZnV5W7m61qWS3g9W81a3jA9KeC2hd6pu-0E3YJRRopWDaZq-54O3SjlpjTTeDkJ557mRZ-TVITdhCR26UMCNLsW4u6rjdWtku0cXB7Tk9HMDWLo5oINpshHSBjtuhG64rA37D8oM07XS-9Q3B-pyQszguyWH2eZtx1m3L65bqa-r--I-7PDLh9xNP8NwpH9r2oEXB5DRHbf_mpd3N3mcPQ</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Ghosh, Arun K</creator><creator>Reddy, Bhavanam Sekhara</creator><creator>Yen, Yu-Chen</creator><creator>Cárdenas, Emilio L</creator><creator>Rao, Kalapala Venkateswara</creator><creator>Downs, Deborah</creator><creator>Huang, Xiangping</creator><creator>Tang, Jordan</creator><creator>Mesecar, Andrew D</creator><general>Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20160101</creationdate><title>Design of potent and highly selective inhibitors for human β-secretase 2 (memapsin 1), a target for type 2 diabetes</title><author>Ghosh, Arun K ; Reddy, Bhavanam Sekhara ; Yen, Yu-Chen ; Cárdenas, Emilio L ; Rao, Kalapala Venkateswara ; Downs, Deborah ; Huang, Xiangping ; Tang, Jordan ; Mesecar, Andrew D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-3ffda6196901d52f63ebc549bd67e8585293d877bb1dfa55c3a838fad25fcf183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Cathepsin D</topic><topic>Design analysis</topic><topic>Diabetes</topic><topic>Human</topic><topic>Inhibitors</topic><topic>Selectivity</topic><topic>Synthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ghosh, Arun K</creatorcontrib><creatorcontrib>Reddy, Bhavanam Sekhara</creatorcontrib><creatorcontrib>Yen, Yu-Chen</creatorcontrib><creatorcontrib>Cárdenas, Emilio L</creatorcontrib><creatorcontrib>Rao, Kalapala Venkateswara</creatorcontrib><creatorcontrib>Downs, Deborah</creatorcontrib><creatorcontrib>Huang, Xiangping</creatorcontrib><creatorcontrib>Tang, Jordan</creatorcontrib><creatorcontrib>Mesecar, Andrew D</creatorcontrib><creatorcontrib>Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Chemical science (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ghosh, Arun K</au><au>Reddy, Bhavanam Sekhara</au><au>Yen, Yu-Chen</au><au>Cárdenas, Emilio L</au><au>Rao, Kalapala Venkateswara</au><au>Downs, Deborah</au><au>Huang, Xiangping</au><au>Tang, Jordan</au><au>Mesecar, Andrew D</au><aucorp>Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design of potent and highly selective inhibitors for human β-secretase 2 (memapsin 1), a target for type 2 diabetes</atitle><jtitle>Chemical science (Cambridge)</jtitle><addtitle>Chem Sci</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>7</volume><issue>5</issue><spage>3117</spage><epage>3122</epage><pages>3117-3122</pages><issn>2041-6520</issn><eissn>2041-6539</eissn><abstract>Design, synthesis and evaluation of very potent and selective β-secretase 2 (memapsin 1, BACE 2) inhibitors are described. The inhibitors were designed specifically to interact with the S2′-site of β-secretase 2 to provide >170 000-fold selectivity over β-secretase (BACE 1) and >15 000-fold selectivity over cathepsin D. BACE 2 is implicated in type 2 diabetes. The studies serve as an important guide to selective BACE 2 inhibitors.
Structure-based design and syntheses of potent and highly selective BACE2 inhibitors are described.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>27347366</pmid><doi>10.1039/c5sc03718b</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | PubMed Central Free; DOAJ Directory of Open Access Journals; PubMed Central Open Access; EZB-FREE-00999 freely available EZB journals |
| subjects | Cathepsin D Design analysis Diabetes Human Inhibitors Selectivity Synthesis |
| title | Design of potent and highly selective inhibitors for human β-secretase 2 (memapsin 1), a target for type 2 diabetes |
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