4-Anilino-6-phenyl-quinoline inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK2)
Compound 2g was found effective in reducing LPS-induced TNFα production in THP-1 cells, in a manner consistent with MK2 enzyme inhibition. A class of inhibitors of mitogen activated protein kinase-activated kinase 2 (MK2) was discovered via high-throughput screening. This compound class demonstrates...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2010-08, Vol.20 (16), p.4738-4740 |
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| container_end_page | 4740 |
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| container_issue | 16 |
| container_start_page | 4738 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 20 |
| creator | Olsson, Henric Sjö, Peter Ersoy, Oguz Kristoffersson, Anna Larsson, Joakim Nordén, Bo |
| description | Compound
2g was found effective in reducing LPS-induced TNFα production in THP-1 cells, in a manner consistent with MK2 enzyme inhibition.
A class of inhibitors of mitogen activated protein kinase-activated kinase 2 (MK2) was discovered via high-throughput screening. This compound class demonstrates activity against the enzyme with sub-μM IC
50 values, and suppresses LPS-induced TNFα levels in THP-1 cells. MK2 inhibition kinetic measurements indicated mixed binding approaching non-ATP competitive inhibition. |
| doi_str_mv | 10.1016/j.bmcl.2010.06.107 |
| format | Article |
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2g was found effective in reducing LPS-induced TNFα production in THP-1 cells, in a manner consistent with MK2 enzyme inhibition.
A class of inhibitors of mitogen activated protein kinase-activated kinase 2 (MK2) was discovered via high-throughput screening. This compound class demonstrates activity against the enzyme with sub-μM IC
50 values, and suppresses LPS-induced TNFα levels in THP-1 cells. MK2 inhibition kinetic measurements indicated mixed binding approaching non-ATP competitive inhibition.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2010.06.107</identifier><identifier>PMID: 20643547</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Aminoquinolines - chemical synthesis ; Aminoquinolines - chemistry ; Aminoquinolines - pharmacology ; Aniline Compounds - chemical synthesis ; Aniline Compounds - chemistry ; Aniline Compounds - pharmacology ; Biological and medical sciences ; Bones, joints and connective tissue. Antiinflammatory agents ; Cell Line ; High-Throughput Screening Assays ; Humans ; Intracellular Signaling Peptides and Proteins - antagonists & inhibitors ; Intracellular Signaling Peptides and Proteins - metabolism ; Kinase inhibitor ; Kinetics ; Lipopolysaccharides - pharmacology ; Medical sciences ; MK2 ; Non-ATP competitive ; Pharmacology. Drug treatments ; Protein Kinase Inhibitors - chemical synthesis ; Protein Kinase Inhibitors - chemistry ; Protein Kinase Inhibitors - pharmacology ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Protein-Serine-Threonine Kinases - metabolism ; Quinolines - chemical synthesis ; Quinolines - chemistry ; Quinolines - pharmacology ; Structure-Activity Relationship ; TNFα ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Bioorganic & medicinal chemistry letters, 2010-08, Vol.20 (16), p.4738-4740</ispartof><rights>2010 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>2010 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-e613b76d3fe574f98cae9a29fbefc7017e5076592d6605cefc91308227ae122a3</citedby><cites>FETCH-LOGICAL-c417t-e613b76d3fe574f98cae9a29fbefc7017e5076592d6605cefc91308227ae122a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X10008942$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23098966$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20643547$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Olsson, Henric</creatorcontrib><creatorcontrib>Sjö, Peter</creatorcontrib><creatorcontrib>Ersoy, Oguz</creatorcontrib><creatorcontrib>Kristoffersson, Anna</creatorcontrib><creatorcontrib>Larsson, Joakim</creatorcontrib><creatorcontrib>Nordén, Bo</creatorcontrib><title>4-Anilino-6-phenyl-quinoline inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK2)</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>Compound
2g was found effective in reducing LPS-induced TNFα production in THP-1 cells, in a manner consistent with MK2 enzyme inhibition.
A class of inhibitors of mitogen activated protein kinase-activated kinase 2 (MK2) was discovered via high-throughput screening. This compound class demonstrates activity against the enzyme with sub-μM IC
50 values, and suppresses LPS-induced TNFα levels in THP-1 cells. MK2 inhibition kinetic measurements indicated mixed binding approaching non-ATP competitive inhibition.</description><subject>Aminoquinolines - chemical synthesis</subject><subject>Aminoquinolines - chemistry</subject><subject>Aminoquinolines - pharmacology</subject><subject>Aniline Compounds - chemical synthesis</subject><subject>Aniline Compounds - chemistry</subject><subject>Aniline Compounds - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Cell Line</subject><subject>High-Throughput Screening Assays</subject><subject>Humans</subject><subject>Intracellular Signaling Peptides and Proteins - antagonists & inhibitors</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Kinase inhibitor</subject><subject>Kinetics</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Medical sciences</subject><subject>MK2</subject><subject>Non-ATP competitive</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Kinase Inhibitors - chemical synthesis</subject><subject>Protein Kinase Inhibitors - chemistry</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein-Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>Quinolines - chemical synthesis</subject><subject>Quinolines - chemistry</subject><subject>Quinolines - pharmacology</subject><subject>Structure-Activity Relationship</subject><subject>TNFα</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9P3DAQxa2qCBbKF-ihyqUqHLwd_4m9lrgg1BZUql5aqTfLcSbF28RZ7CwS3x6vdoET5eTxm98bjeYR8p7BnAFTn5fzZvD9nEMRQBVNvyEzJpWkQkL9lszAKKALI_8ckMOclwBMgpT75ICDkqKWekZ6Sc9j6EMcqaKrG4z3Pb1dl2-RsArxJjRhGlOuxq4aSvUXY-X8FO7chG21SuOEIVb_QnQZ6UuNilcnP77z03dkr3N9xuPde0R-f_3y6-KSXv_8dnVxfk29ZHqiqJhotGpFh7WWnVl4h8Zx0zXYeQ1MYw1a1Ya3SkHti2iYgAXn2iHj3Ikj8mk7t6xxu8Y82SFkj33vIo7rbHUtayV0cb1KSgPcGMELybekT2POCTu7SmFw6d4ysJs47NJu4rCbOCyoouli-rAbv24GbJ8sj_cvwMcd4LJ3fZdc9CE_cwLMwihVuLMth-VsdwGTzT5g9NiGhH6y7Rj-t8cDwMSoXA</recordid><startdate>20100815</startdate><enddate>20100815</enddate><creator>Olsson, Henric</creator><creator>Sjö, Peter</creator><creator>Ersoy, Oguz</creator><creator>Kristoffersson, Anna</creator><creator>Larsson, Joakim</creator><creator>Nordén, Bo</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</scope><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><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20100815</creationdate><title>4-Anilino-6-phenyl-quinoline inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK2)</title><author>Olsson, Henric ; Sjö, Peter ; Ersoy, Oguz ; Kristoffersson, Anna ; Larsson, Joakim ; Nordén, Bo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-e613b76d3fe574f98cae9a29fbefc7017e5076592d6605cefc91308227ae122a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Aminoquinolines - chemical synthesis</topic><topic>Aminoquinolines - chemistry</topic><topic>Aminoquinolines - pharmacology</topic><topic>Aniline Compounds - chemical synthesis</topic><topic>Aniline Compounds - chemistry</topic><topic>Aniline Compounds - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Bones, joints and connective tissue. Antiinflammatory agents</topic><topic>Cell Line</topic><topic>High-Throughput Screening Assays</topic><topic>Humans</topic><topic>Intracellular Signaling Peptides and Proteins - antagonists & inhibitors</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Kinase inhibitor</topic><topic>Kinetics</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Medical sciences</topic><topic>MK2</topic><topic>Non-ATP competitive</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Kinase Inhibitors - chemical synthesis</topic><topic>Protein Kinase Inhibitors - chemistry</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Protein-Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>Quinolines - chemical synthesis</topic><topic>Quinolines - chemistry</topic><topic>Quinolines - pharmacology</topic><topic>Structure-Activity Relationship</topic><topic>TNFα</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Olsson, Henric</creatorcontrib><creatorcontrib>Sjö, Peter</creatorcontrib><creatorcontrib>Ersoy, Oguz</creatorcontrib><creatorcontrib>Kristoffersson, Anna</creatorcontrib><creatorcontrib>Larsson, Joakim</creatorcontrib><creatorcontrib>Nordén, Bo</creatorcontrib><collection>Pascal-Francis</collection><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><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Olsson, Henric</au><au>Sjö, Peter</au><au>Ersoy, Oguz</au><au>Kristoffersson, Anna</au><au>Larsson, Joakim</au><au>Nordén, Bo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>4-Anilino-6-phenyl-quinoline inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK2)</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2010-08-15</date><risdate>2010</risdate><volume>20</volume><issue>16</issue><spage>4738</spage><epage>4740</epage><pages>4738-4740</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>Compound
2g was found effective in reducing LPS-induced TNFα production in THP-1 cells, in a manner consistent with MK2 enzyme inhibition.
A class of inhibitors of mitogen activated protein kinase-activated kinase 2 (MK2) was discovered via high-throughput screening. This compound class demonstrates activity against the enzyme with sub-μM IC
50 values, and suppresses LPS-induced TNFα levels in THP-1 cells. MK2 inhibition kinetic measurements indicated mixed binding approaching non-ATP competitive inhibition.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>20643547</pmid><doi>10.1016/j.bmcl.2010.06.107</doi><tpages>3</tpages></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Aminoquinolines - chemical synthesis Aminoquinolines - chemistry Aminoquinolines - pharmacology Aniline Compounds - chemical synthesis Aniline Compounds - chemistry Aniline Compounds - pharmacology Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Cell Line High-Throughput Screening Assays Humans Intracellular Signaling Peptides and Proteins - antagonists & inhibitors Intracellular Signaling Peptides and Proteins - metabolism Kinase inhibitor Kinetics Lipopolysaccharides - pharmacology Medical sciences MK2 Non-ATP competitive Pharmacology. Drug treatments Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology Protein-Serine-Threonine Kinases - antagonists & inhibitors Protein-Serine-Threonine Kinases - metabolism Quinolines - chemical synthesis Quinolines - chemistry Quinolines - pharmacology Structure-Activity Relationship TNFα Tumor Necrosis Factor-alpha - metabolism |
| title | 4-Anilino-6-phenyl-quinoline inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK2) |
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