Discovery of Novel Ansamycins Possessing Potent Inhibitory Activity in a Cell-based Oncostatin M Signalling Assay
We describe the isolation and characterisation of novel non-benzoquinone ansamycin metabolites related to geldanamycin from a culture of Streptomyces sp. S6699. The compounds possess potent inhibitory activity in a cell-based assay measuring inhibition of oncostatin M signalling in a reporter cell l...
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creator | STEAD, PAUL LATIF, SHAZIA BLACKABY, ANDREW P. SIDEBOTTOM, PHILIP J. DEAKIN, ANGELA TAYLOR, NICHOLAS L. LIFE, PAUL SPAULL, JOHN BURRELL, FIONA JONES, ROSIE LEWIS, JANE DAVIDSON, IAN MANDER, THOMAS |
description | We describe the isolation and characterisation of novel non-benzoquinone ansamycin metabolites related to geldanamycin from a culture of Streptomyces sp. S6699. The compounds possess potent inhibitory activity in a cell-based assay measuring inhibition of oncostatin M signalling in a reporter cell line utilising a secreted placental alkaline phosphatase (sPAP) readout. In this paper we report the isolation and structure elucidation of the compounds and describe some of their biological properties. |
doi_str_mv | 10.7164/antibiotics.53.657 |
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S6699. The compounds possess potent inhibitory activity in a cell-based assay measuring inhibition of oncostatin M signalling in a reporter cell line utilising a secreted placental alkaline phosphatase (sPAP) readout. In this paper we report the isolation and structure elucidation of the compounds and describe some of their biological properties.</description><identifier>ISSN: 0021-8820</identifier><identifier>EISSN: 1881-1469</identifier><identifier>DOI: 10.7164/antibiotics.53.657</identifier><identifier>PMID: 10994806</identifier><identifier>CODEN: JANTAJ</identifier><language>eng</language><publisher>Tokyo: JAPAN ANTIBIOTICS RESEARCH ASSOCIATION</publisher><subject>Alkaline phosphatase ; Alkaline Phosphatase - drug effects ; Alkaline Phosphatase - genetics ; Alkaline Phosphatase - metabolism ; ansamycin ; Ansamycins ; Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - metabolism ; Anti-Bacterial Agents - pharmacology ; Antibiotics (antibacterial agents, antifungal agents) ; Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents ; Applied microbiology ; Benzoquinones ; Biological and medical sciences ; Cell Line ; Cell Survival - drug effects ; Drug Evaluation, Preclinical - methods ; Fundamental and applied biological sciences. Psychology ; Humans ; Inhibitory Concentration 50 ; Interleukin-6 - metabolism ; Interleukin-6 - pharmacology ; Lactams, Macrocyclic ; Lung - cytology ; Lung - drug effects ; Microbiology ; Oncostatin M ; Peptides - metabolism ; Protein Biosynthesis ; Proteins - drug effects ; Quinones - chemistry ; Quinones - metabolism ; Quinones - pharmacology ; Recombinant Proteins - drug effects ; Recombinant Proteins - genetics ; Recombinant Proteins - metabolism ; Rifabutin - chemistry ; Rifabutin - pharmacology ; Signal Transduction ; Streptomyces ; Streptomyces - metabolism</subject><ispartof>The Journal of Antibiotics, 2000/07/25, Vol.53(7), pp.657-663</ispartof><rights>Japan Antibiotics Research Association</rights><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c566t-883ffc172348ae6bc3426f2103ddd4d6fbaeb260443df858532d8ba27128df3c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1483391$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10994806$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>STEAD, PAUL</creatorcontrib><creatorcontrib>LATIF, SHAZIA</creatorcontrib><creatorcontrib>BLACKABY, ANDREW P.</creatorcontrib><creatorcontrib>SIDEBOTTOM, PHILIP J.</creatorcontrib><creatorcontrib>DEAKIN, ANGELA</creatorcontrib><creatorcontrib>TAYLOR, NICHOLAS L.</creatorcontrib><creatorcontrib>LIFE, PAUL</creatorcontrib><creatorcontrib>SPAULL, JOHN</creatorcontrib><creatorcontrib>BURRELL, FIONA</creatorcontrib><creatorcontrib>JONES, ROSIE</creatorcontrib><creatorcontrib>LEWIS, JANE</creatorcontrib><creatorcontrib>DAVIDSON, IAN</creatorcontrib><creatorcontrib>MANDER, THOMAS</creatorcontrib><title>Discovery of Novel Ansamycins Possessing Potent Inhibitory Activity in a Cell-based Oncostatin M Signalling Assay</title><title>Journal of antibiotics</title><addtitle>J. Antibiot.</addtitle><description>We describe the isolation and characterisation of novel non-benzoquinone ansamycin metabolites related to geldanamycin from a culture of Streptomyces sp. S6699. The compounds possess potent inhibitory activity in a cell-based assay measuring inhibition of oncostatin M signalling in a reporter cell line utilising a secreted placental alkaline phosphatase (sPAP) readout. In this paper we report the isolation and structure elucidation of the compounds and describe some of their biological properties.</description><subject>Alkaline phosphatase</subject><subject>Alkaline Phosphatase - drug effects</subject><subject>Alkaline Phosphatase - genetics</subject><subject>Alkaline Phosphatase - metabolism</subject><subject>ansamycin</subject><subject>Ansamycins</subject><subject>Anti-Bacterial Agents - chemistry</subject><subject>Anti-Bacterial Agents - metabolism</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibiotics (antibacterial agents, antifungal agents)</subject><subject>Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents</subject><subject>Applied microbiology</subject><subject>Benzoquinones</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cell Survival - drug effects</subject><subject>Drug Evaluation, Preclinical - methods</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Inhibitory Concentration 50</subject><subject>Interleukin-6 - metabolism</subject><subject>Interleukin-6 - pharmacology</subject><subject>Lactams, Macrocyclic</subject><subject>Lung - cytology</subject><subject>Lung - drug effects</subject><subject>Microbiology</subject><subject>Oncostatin M</subject><subject>Peptides - metabolism</subject><subject>Protein Biosynthesis</subject><subject>Proteins - drug effects</subject><subject>Quinones - chemistry</subject><subject>Quinones - metabolism</subject><subject>Quinones - pharmacology</subject><subject>Recombinant Proteins - drug effects</subject><subject>Recombinant Proteins - genetics</subject><subject>Recombinant Proteins - metabolism</subject><subject>Rifabutin - chemistry</subject><subject>Rifabutin - pharmacology</subject><subject>Signal Transduction</subject><subject>Streptomyces</subject><subject>Streptomyces - metabolism</subject><issn>0021-8820</issn><issn>1881-1469</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkEtvGyEUhVHVqHHc_oEuKhZVd-PwGmCWlvtI1LSplHSNGAYcojGTzMWR5t8Xa6zUG7iC755z70HoIyUrRaW4tCnHNg45OljVfCVr9QYtqNa0okI2b9GCEEYrrRk5RxcAj4RwxZV-h84paRqhiVyg568R3PDixwkPAf8uVY_XCexucjEB_jMAeICYtqXMPmV8nR6KaR5Kw9rl-BLzhGPCFm9831etBd_h2-QGyDaX91_4Lm6T7fuDxBrATu_RWbA9-A_He4n-fv92v7mqbm5_XG_WN5WrpcxlbB6Co4pxoa2XreOCycAo4V3XiU6G1vqWSSIE74Kudc1Zp1vLFGW6C9zxJfoy6z6Nw_PeQza7smoZ0iY_7MFQpThTxWaJ2Ay6sWw7-mCexriz42QoMYegzUnQpuamBF2aPh3V9-3Odyctc7IF-HwELDjbh9EmF-E_JzTnDS3Yzxl7LIFt_eu_HYtb70-taSP1wV7NR5nilXIPdjQ-8X9y6aaD</recordid><startdate>20000701</startdate><enddate>20000701</enddate><creator>STEAD, PAUL</creator><creator>LATIF, SHAZIA</creator><creator>BLACKABY, ANDREW P.</creator><creator>SIDEBOTTOM, PHILIP J.</creator><creator>DEAKIN, ANGELA</creator><creator>TAYLOR, NICHOLAS L.</creator><creator>LIFE, PAUL</creator><creator>SPAULL, JOHN</creator><creator>BURRELL, FIONA</creator><creator>JONES, ROSIE</creator><creator>LEWIS, JANE</creator><creator>DAVIDSON, IAN</creator><creator>MANDER, THOMAS</creator><general>JAPAN ANTIBIOTICS RESEARCH ASSOCIATION</general><general>Japan Antibiotics Research Association</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>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20000701</creationdate><title>Discovery of Novel Ansamycins Possessing Potent Inhibitory Activity in a Cell-based Oncostatin M Signalling Assay</title><author>STEAD, PAUL ; LATIF, SHAZIA ; BLACKABY, ANDREW P. ; SIDEBOTTOM, PHILIP J. ; DEAKIN, ANGELA ; TAYLOR, NICHOLAS L. ; LIFE, PAUL ; SPAULL, JOHN ; BURRELL, FIONA ; JONES, ROSIE ; LEWIS, JANE ; DAVIDSON, IAN ; MANDER, THOMAS</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c566t-883ffc172348ae6bc3426f2103ddd4d6fbaeb260443df858532d8ba27128df3c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Alkaline phosphatase</topic><topic>Alkaline Phosphatase - drug effects</topic><topic>Alkaline Phosphatase - genetics</topic><topic>Alkaline Phosphatase - metabolism</topic><topic>ansamycin</topic><topic>Ansamycins</topic><topic>Anti-Bacterial Agents - chemistry</topic><topic>Anti-Bacterial Agents - metabolism</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antibiotics (antibacterial agents, antifungal agents)</topic><topic>Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents</topic><topic>Applied microbiology</topic><topic>Benzoquinones</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Cell Survival - drug effects</topic><topic>Drug Evaluation, Preclinical - methods</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Inhibitory Concentration 50</topic><topic>Interleukin-6 - metabolism</topic><topic>Interleukin-6 - pharmacology</topic><topic>Lactams, Macrocyclic</topic><topic>Lung - cytology</topic><topic>Lung - drug effects</topic><topic>Microbiology</topic><topic>Oncostatin M</topic><topic>Peptides - metabolism</topic><topic>Protein Biosynthesis</topic><topic>Proteins - drug effects</topic><topic>Quinones - chemistry</topic><topic>Quinones - metabolism</topic><topic>Quinones - pharmacology</topic><topic>Recombinant Proteins - drug effects</topic><topic>Recombinant Proteins - genetics</topic><topic>Recombinant Proteins - metabolism</topic><topic>Rifabutin - chemistry</topic><topic>Rifabutin - pharmacology</topic><topic>Signal Transduction</topic><topic>Streptomyces</topic><topic>Streptomyces - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>STEAD, PAUL</creatorcontrib><creatorcontrib>LATIF, SHAZIA</creatorcontrib><creatorcontrib>BLACKABY, ANDREW P.</creatorcontrib><creatorcontrib>SIDEBOTTOM, PHILIP J.</creatorcontrib><creatorcontrib>DEAKIN, ANGELA</creatorcontrib><creatorcontrib>TAYLOR, NICHOLAS L.</creatorcontrib><creatorcontrib>LIFE, PAUL</creatorcontrib><creatorcontrib>SPAULL, JOHN</creatorcontrib><creatorcontrib>BURRELL, FIONA</creatorcontrib><creatorcontrib>JONES, ROSIE</creatorcontrib><creatorcontrib>LEWIS, JANE</creatorcontrib><creatorcontrib>DAVIDSON, IAN</creatorcontrib><creatorcontrib>MANDER, THOMAS</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Journal of antibiotics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>STEAD, PAUL</au><au>LATIF, SHAZIA</au><au>BLACKABY, ANDREW P.</au><au>SIDEBOTTOM, PHILIP J.</au><au>DEAKIN, ANGELA</au><au>TAYLOR, NICHOLAS L.</au><au>LIFE, PAUL</au><au>SPAULL, JOHN</au><au>BURRELL, FIONA</au><au>JONES, ROSIE</au><au>LEWIS, JANE</au><au>DAVIDSON, IAN</au><au>MANDER, THOMAS</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of Novel Ansamycins Possessing Potent Inhibitory Activity in a Cell-based Oncostatin M Signalling Assay</atitle><jtitle>Journal of antibiotics</jtitle><addtitle>J. Antibiot.</addtitle><date>2000-07-01</date><risdate>2000</risdate><volume>53</volume><issue>7</issue><spage>657</spage><epage>663</epage><pages>657-663</pages><issn>0021-8820</issn><eissn>1881-1469</eissn><coden>JANTAJ</coden><abstract>We describe the isolation and characterisation of novel non-benzoquinone ansamycin metabolites related to geldanamycin from a culture of Streptomyces sp. S6699. The compounds possess potent inhibitory activity in a cell-based assay measuring inhibition of oncostatin M signalling in a reporter cell line utilising a secreted placental alkaline phosphatase (sPAP) readout. In this paper we report the isolation and structure elucidation of the compounds and describe some of their biological properties.</abstract><cop>Tokyo</cop><pub>JAPAN ANTIBIOTICS RESEARCH ASSOCIATION</pub><pmid>10994806</pmid><doi>10.7164/antibiotics.53.657</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Alkaline phosphatase Alkaline Phosphatase - drug effects Alkaline Phosphatase - genetics Alkaline Phosphatase - metabolism ansamycin Ansamycins Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - metabolism Anti-Bacterial Agents - pharmacology Antibiotics (antibacterial agents, antifungal agents) Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents Applied microbiology Benzoquinones Biological and medical sciences Cell Line Cell Survival - drug effects Drug Evaluation, Preclinical - methods Fundamental and applied biological sciences. Psychology Humans Inhibitory Concentration 50 Interleukin-6 - metabolism Interleukin-6 - pharmacology Lactams, Macrocyclic Lung - cytology Lung - drug effects Microbiology Oncostatin M Peptides - metabolism Protein Biosynthesis Proteins - drug effects Quinones - chemistry Quinones - metabolism Quinones - pharmacology Recombinant Proteins - drug effects Recombinant Proteins - genetics Recombinant Proteins - metabolism Rifabutin - chemistry Rifabutin - pharmacology Signal Transduction Streptomyces Streptomyces - metabolism |
title | Discovery of Novel Ansamycins Possessing Potent Inhibitory Activity in a Cell-based Oncostatin M Signalling Assay |
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