Trypsin inhibitors for the treatment of pancreatitis
[Display omitted] Proline-based trypsin inhibitors occupying the S1–S2–S1′ region were identified by an HTS screening campaign. It was discovered that truncation of the P1′ moiety and appropriate extension into the S4 region led to highly potent trypsin inhibitors with excellent selectivity against...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2016-09, Vol.26 (17), p.4340-4344 |
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| container_end_page | 4344 |
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| container_issue | 17 |
| container_start_page | 4340 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 26 |
| creator | Brandl, Trixi Simic, Oliver Skaanderup, Philip R. Namoto, Kenji Berst, Frederic Ehrhardt, Claus Schiering, Nikolaus Mueller, Irene Woelcke, Julian |
| description | [Display omitted]
Proline-based trypsin inhibitors occupying the S1–S2–S1′ region were identified by an HTS screening campaign. It was discovered that truncation of the P1′ moiety and appropriate extension into the S4 region led to highly potent trypsin inhibitors with excellent selectivity against related serine proteases and a favorable hERG profile. |
| doi_str_mv | 10.1016/j.bmcl.2016.07.029 |
| format | Article |
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Proline-based trypsin inhibitors occupying the S1–S2–S1′ region were identified by an HTS screening campaign. It was discovered that truncation of the P1′ moiety and appropriate extension into the S4 region led to highly potent trypsin inhibitors with excellent selectivity against related serine proteases and a favorable hERG profile.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2016.07.029</identifier><identifier>PMID: 27476144</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Crystallography, X-Ray ; Enzyme Activation - drug effects ; hERG inhibition ; Humans ; Inhibitory Concentration 50 ; Molecular Structure ; Pancreatitis ; Pancreatitis - drug therapy ; Structure-Activity Relationship ; Trypsin inhibitor ; Trypsin Inhibitors - chemical synthesis ; Trypsin Inhibitors - chemistry ; Trypsin Inhibitors - pharmacology ; Trypsin Inhibitors - therapeutic use ; X-ray crystal structure</subject><ispartof>Bioorganic & medicinal chemistry letters, 2016-09, Vol.26 (17), p.4340-4344</ispartof><rights>2016 Elsevier Ltd</rights><rights>Copyright © 2016 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-ca6e7bc372a79567b9be6d928f0cfc6c9126e73131ac4f7161c820787b34de223</citedby><cites>FETCH-LOGICAL-c356t-ca6e7bc372a79567b9be6d928f0cfc6c9126e73131ac4f7161c820787b34de223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2016.07.029$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27476144$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Brandl, Trixi</creatorcontrib><creatorcontrib>Simic, Oliver</creatorcontrib><creatorcontrib>Skaanderup, Philip R.</creatorcontrib><creatorcontrib>Namoto, Kenji</creatorcontrib><creatorcontrib>Berst, Frederic</creatorcontrib><creatorcontrib>Ehrhardt, Claus</creatorcontrib><creatorcontrib>Schiering, Nikolaus</creatorcontrib><creatorcontrib>Mueller, Irene</creatorcontrib><creatorcontrib>Woelcke, Julian</creatorcontrib><title>Trypsin inhibitors for the treatment of pancreatitis</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
Proline-based trypsin inhibitors occupying the S1–S2–S1′ region were identified by an HTS screening campaign. It was discovered that truncation of the P1′ moiety and appropriate extension into the S4 region led to highly potent trypsin inhibitors with excellent selectivity against related serine proteases and a favorable hERG profile.</description><subject>Crystallography, X-Ray</subject><subject>Enzyme Activation - drug effects</subject><subject>hERG inhibition</subject><subject>Humans</subject><subject>Inhibitory Concentration 50</subject><subject>Molecular Structure</subject><subject>Pancreatitis</subject><subject>Pancreatitis - drug therapy</subject><subject>Structure-Activity Relationship</subject><subject>Trypsin inhibitor</subject><subject>Trypsin Inhibitors - chemical synthesis</subject><subject>Trypsin Inhibitors - chemistry</subject><subject>Trypsin Inhibitors - pharmacology</subject><subject>Trypsin Inhibitors - therapeutic use</subject><subject>X-ray crystal structure</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LxDAQhoMo7rr6BzxIj15a87VJCl5k8QsWvKzgLaTplM3SNjXJCv57W3b16Glm4HlfmAeha4ILgom42xVVZ9uCjnuBZYFpeYLmhAueM46Xp2iOS4FzVfKPGbqIcYcx4ZjzczSjkktBOJ8jvgnfQ3R95vqtq1zyIWaND1naQpYCmNRBnzLfZIPp7XS75OIlOmtMG-HqOBfo_elxs3rJ12_Pr6uHdW7ZUqTcGgGyskxSI8ulkFVZgahLqhpsGytsSegIMMKIsbyRRBCrKJZKVozXQClboNtD7xD85x5i0p2LFtrW9OD3URNFiOKMKjWi9IDa4GMM0OghuM6Eb02wnmzpnZ5s6cmWxlKPtsbQzbF_X3VQ_0V-9YzA_QGA8csvB0FH66C3ULsANunau__6fwDlcHq5</recordid><startdate>20160901</startdate><enddate>20160901</enddate><creator>Brandl, Trixi</creator><creator>Simic, Oliver</creator><creator>Skaanderup, Philip R.</creator><creator>Namoto, Kenji</creator><creator>Berst, Frederic</creator><creator>Ehrhardt, Claus</creator><creator>Schiering, Nikolaus</creator><creator>Mueller, Irene</creator><creator>Woelcke, Julian</creator><general>Elsevier Ltd</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>20160901</creationdate><title>Trypsin inhibitors for the treatment of pancreatitis</title><author>Brandl, Trixi ; Simic, Oliver ; Skaanderup, Philip R. ; Namoto, Kenji ; Berst, Frederic ; Ehrhardt, Claus ; Schiering, Nikolaus ; Mueller, Irene ; Woelcke, Julian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-ca6e7bc372a79567b9be6d928f0cfc6c9126e73131ac4f7161c820787b34de223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Crystallography, X-Ray</topic><topic>Enzyme Activation - drug effects</topic><topic>hERG inhibition</topic><topic>Humans</topic><topic>Inhibitory Concentration 50</topic><topic>Molecular Structure</topic><topic>Pancreatitis</topic><topic>Pancreatitis - drug therapy</topic><topic>Structure-Activity Relationship</topic><topic>Trypsin inhibitor</topic><topic>Trypsin Inhibitors - chemical synthesis</topic><topic>Trypsin Inhibitors - chemistry</topic><topic>Trypsin Inhibitors - pharmacology</topic><topic>Trypsin Inhibitors - therapeutic use</topic><topic>X-ray crystal structure</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Brandl, Trixi</creatorcontrib><creatorcontrib>Simic, Oliver</creatorcontrib><creatorcontrib>Skaanderup, Philip R.</creatorcontrib><creatorcontrib>Namoto, Kenji</creatorcontrib><creatorcontrib>Berst, Frederic</creatorcontrib><creatorcontrib>Ehrhardt, Claus</creatorcontrib><creatorcontrib>Schiering, Nikolaus</creatorcontrib><creatorcontrib>Mueller, Irene</creatorcontrib><creatorcontrib>Woelcke, Julian</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>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Brandl, Trixi</au><au>Simic, Oliver</au><au>Skaanderup, Philip R.</au><au>Namoto, Kenji</au><au>Berst, Frederic</au><au>Ehrhardt, Claus</au><au>Schiering, Nikolaus</au><au>Mueller, Irene</au><au>Woelcke, Julian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Trypsin inhibitors for the treatment of pancreatitis</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2016-09-01</date><risdate>2016</risdate><volume>26</volume><issue>17</issue><spage>4340</spage><epage>4344</epage><pages>4340-4344</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
Proline-based trypsin inhibitors occupying the S1–S2–S1′ region were identified by an HTS screening campaign. It was discovered that truncation of the P1′ moiety and appropriate extension into the S4 region led to highly potent trypsin inhibitors with excellent selectivity against related serine proteases and a favorable hERG profile.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>27476144</pmid><doi>10.1016/j.bmcl.2016.07.029</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2016-09, Vol.26 (17), p.4340-4344 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Crystallography, X-Ray Enzyme Activation - drug effects hERG inhibition Humans Inhibitory Concentration 50 Molecular Structure Pancreatitis Pancreatitis - drug therapy Structure-Activity Relationship Trypsin inhibitor Trypsin Inhibitors - chemical synthesis Trypsin Inhibitors - chemistry Trypsin Inhibitors - pharmacology Trypsin Inhibitors - therapeutic use X-ray crystal structure |
| title | Trypsin inhibitors for the treatment of pancreatitis |
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