Selectivity of Microbial Acyl-CoA : cholesterol Acyltransferase Inhibitors toward Isozymes
The selectivity of microbial inhibitors of acyl-CoA : cholesterol acyltransferase (ACAT) toward the two isozymes, ACAT1 and ACAT2, was assessed in cell-based assays. Purpactin A (IC 50 values of ACAT1 vs . IC 50 values of ACAT2; 2.5 μM vs . 1.5 μM), terpendole C (10 μM vs . 10 μM), glisoprenin A (4....
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| Veröffentlicht in: | Journal of antibiotics 2007-01, Vol.60 (1), p.43-51 |
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| creator | Ohshiro, Taichi Rudel, Lawrence L Ōmura, Satoshi Tomoda, Hiroshi |
| description | The selectivity of microbial inhibitors of acyl-CoA : cholesterol acyltransferase (ACAT) toward the two isozymes, ACAT1 and ACAT2, was assessed in cell-based assays. Purpactin A (IC
50
values of ACAT1
vs
. IC
50
values of ACAT2; 2.5 μM
vs
. 1.5 μM), terpendole C (10 μM
vs
. 10 μM), glisoprenin A (4.3 μM
vs
. 10 μM), spylidone (25 μM
vs
. 5.0 μM) and synthetic CL-283,546 (0.1 μM
vs
. 0.09 μM) inhibited ACAT1 and ACAT2 to similar extents. Beauveriolides I (0.6 μM
vs
. 20 μM) and III (0.9 μM
vs
. >20 μM) inhibited ACAT1 rather selectively, while pyripyropenes A (>80 μM
vs
. 0.07 μM), B (48 μM
vs
. 2.0 μM), C (32 μM
vs
. 0.36 μM) and D (38 μM
vs
. 1.5 μM) showed selective inhibition against ACAT2. In particular, pyripyropene A was found to be the most selective ACAT2 inhibitor with a selective index of more than 1,000. |
| doi_str_mv | 10.1038/ja.2007.6 |
| format | Article |
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50
values of ACAT1
vs
. IC
50
values of ACAT2; 2.5 μM
vs
. 1.5 μM), terpendole C (10 μM
vs
. 10 μM), glisoprenin A (4.3 μM
vs
. 10 μM), spylidone (25 μM
vs
. 5.0 μM) and synthetic CL-283,546 (0.1 μM
vs
. 0.09 μM) inhibited ACAT1 and ACAT2 to similar extents. Beauveriolides I (0.6 μM
vs
. 20 μM) and III (0.9 μM
vs
. >20 μM) inhibited ACAT1 rather selectively, while pyripyropenes A (>80 μM
vs
. 0.07 μM), B (48 μM
vs
. 2.0 μM), C (32 μM
vs
. 0.36 μM) and D (38 μM
vs
. 1.5 μM) showed selective inhibition against ACAT2. In particular, pyripyropene A was found to be the most selective ACAT2 inhibitor with a selective index of more than 1,000.</description><identifier>ISSN: 0021-8820</identifier><identifier>EISSN: 1881-1469</identifier><identifier>DOI: 10.1038/ja.2007.6</identifier><identifier>PMID: 17390588</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Animals ; Bacteriology ; Biomedical and Life Sciences ; Bioorganic Chemistry ; CHO Cells ; Cholesterol ; Cholesterol Esters - biosynthesis ; Cricetinae ; Cricetulus ; Depsipeptides - pharmacology ; Diterpenes - pharmacology ; Enzyme Inhibitors - pharmacology ; Fatty Alcohols - pharmacology ; Heterocyclic Compounds, 3-Ring - pharmacology ; Indoles - pharmacology ; Isoenzymes - antagonists & inhibitors ; Life Sciences ; Macrophages, Peritoneal - drug effects ; Macrophages, Peritoneal - metabolism ; Medicinal Chemistry ; Mice ; Microbiology ; Molecular Structure ; Organic Chemistry ; original-article ; Phenanthrenes - pharmacology ; Phenylurea Compounds - pharmacology ; Pyridines - pharmacology ; Sesquiterpenes - pharmacology ; Spiro Compounds - pharmacology ; Sterol O-Acyltransferase - antagonists & inhibitors ; Sterol O-Acyltransferase 2</subject><ispartof>Journal of antibiotics, 2007-01, Vol.60 (1), p.43-51</ispartof><rights>Japan Antibiotics Research Association 2007</rights><rights>Copyright Nature Publishing Group Jan 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c500t-8bfdf080aa9365939ac77a8e811dd84f21d10a5894b4c9b4c10e91fad7251fb13</citedby><cites>FETCH-LOGICAL-c500t-8bfdf080aa9365939ac77a8e811dd84f21d10a5894b4c9b4c10e91fad7251fb13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17390588$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ohshiro, Taichi</creatorcontrib><creatorcontrib>Rudel, Lawrence L</creatorcontrib><creatorcontrib>Ōmura, Satoshi</creatorcontrib><creatorcontrib>Tomoda, Hiroshi</creatorcontrib><title>Selectivity of Microbial Acyl-CoA : cholesterol Acyltransferase Inhibitors toward Isozymes</title><title>Journal of antibiotics</title><addtitle>J Antibiot</addtitle><addtitle>J Antibiot (Tokyo)</addtitle><description>The selectivity of microbial inhibitors of acyl-CoA : cholesterol acyltransferase (ACAT) toward the two isozymes, ACAT1 and ACAT2, was assessed in cell-based assays. Purpactin A (IC
50
values of ACAT1
vs
. IC
50
values of ACAT2; 2.5 μM
vs
. 1.5 μM), terpendole C (10 μM
vs
. 10 μM), glisoprenin A (4.3 μM
vs
. 10 μM), spylidone (25 μM
vs
. 5.0 μM) and synthetic CL-283,546 (0.1 μM
vs
. 0.09 μM) inhibited ACAT1 and ACAT2 to similar extents. Beauveriolides I (0.6 μM
vs
. 20 μM) and III (0.9 μM
vs
. >20 μM) inhibited ACAT1 rather selectively, while pyripyropenes A (>80 μM
vs
. 0.07 μM), B (48 μM
vs
. 2.0 μM), C (32 μM
vs
. 0.36 μM) and D (38 μM
vs
. 1.5 μM) showed selective inhibition against ACAT2. In particular, pyripyropene A was found to be the most selective ACAT2 inhibitor with a selective index of more than 1,000.</description><subject>Animals</subject><subject>Bacteriology</subject><subject>Biomedical and Life Sciences</subject><subject>Bioorganic Chemistry</subject><subject>CHO Cells</subject><subject>Cholesterol</subject><subject>Cholesterol Esters - biosynthesis</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Depsipeptides - pharmacology</subject><subject>Diterpenes - pharmacology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fatty Alcohols - pharmacology</subject><subject>Heterocyclic Compounds, 3-Ring - pharmacology</subject><subject>Indoles - pharmacology</subject><subject>Isoenzymes - antagonists & inhibitors</subject><subject>Life Sciences</subject><subject>Macrophages, Peritoneal - drug effects</subject><subject>Macrophages, Peritoneal - metabolism</subject><subject>Medicinal Chemistry</subject><subject>Mice</subject><subject>Microbiology</subject><subject>Molecular Structure</subject><subject>Organic Chemistry</subject><subject>original-article</subject><subject>Phenanthrenes - pharmacology</subject><subject>Phenylurea Compounds - pharmacology</subject><subject>Pyridines - pharmacology</subject><subject>Sesquiterpenes - pharmacology</subject><subject>Spiro Compounds - pharmacology</subject><subject>Sterol O-Acyltransferase - antagonists & inhibitors</subject><subject>Sterol O-Acyltransferase 2</subject><issn>0021-8820</issn><issn>1881-1469</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNplkM1L9DAQh4Moun4c_AdeCoKg0HWm2TYTb8vix4LiQb14CWmbaJdu45t0lfWvN7ILih6GgZmH3wwPY4cIQwROZzM9zADEsNhgAyTCFEeF3GQDgAxTogx22G4IMwAuuKBttoOCS8iJBuzp3rSm6pu3pl8mzia3TeVd2eg2GVfLNp24cXKeVC-uNaE33q3GvdddsMbrYJJp99KUTe98SHr3rn2dTIP7WM5N2GdbVrfBHKz7Hnu8vHiYXKc3d1fTyfgmrXKAPqXS1hYItJa8yCWXuhJCkyHEuqaRzbBG0DnJUTmqZCwEI9HqWmQ52hL5Hjte5b56938R_1TzJlSmbXVn3CIoARy5FBTBo1_gzC18F39TKEgQFBnISJ2sqCgiBG-sevXNXPulQlBfutVMqy_dqojsv3Xiopyb-ptc-43A6QoIcdU9G__j5J-0T2EJiJQ</recordid><startdate>20070101</startdate><enddate>20070101</enddate><creator>Ohshiro, Taichi</creator><creator>Rudel, Lawrence L</creator><creator>Ōmura, Satoshi</creator><creator>Tomoda, Hiroshi</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7QL</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20070101</creationdate><title>Selectivity of Microbial Acyl-CoA : cholesterol Acyltransferase Inhibitors toward Isozymes</title><author>Ohshiro, Taichi ; Rudel, Lawrence L ; Ōmura, Satoshi ; Tomoda, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c500t-8bfdf080aa9365939ac77a8e811dd84f21d10a5894b4c9b4c10e91fad7251fb13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Bacteriology</topic><topic>Biomedical and Life Sciences</topic><topic>Bioorganic Chemistry</topic><topic>CHO Cells</topic><topic>Cholesterol</topic><topic>Cholesterol Esters - biosynthesis</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>Depsipeptides - pharmacology</topic><topic>Diterpenes - pharmacology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fatty Alcohols - pharmacology</topic><topic>Heterocyclic Compounds, 3-Ring - pharmacology</topic><topic>Indoles - pharmacology</topic><topic>Isoenzymes - antagonists & inhibitors</topic><topic>Life Sciences</topic><topic>Macrophages, Peritoneal - drug effects</topic><topic>Macrophages, Peritoneal - metabolism</topic><topic>Medicinal Chemistry</topic><topic>Mice</topic><topic>Microbiology</topic><topic>Molecular Structure</topic><topic>Organic Chemistry</topic><topic>original-article</topic><topic>Phenanthrenes - pharmacology</topic><topic>Phenylurea Compounds - pharmacology</topic><topic>Pyridines - pharmacology</topic><topic>Sesquiterpenes - pharmacology</topic><topic>Spiro Compounds - pharmacology</topic><topic>Sterol O-Acyltransferase - antagonists & inhibitors</topic><topic>Sterol O-Acyltransferase 2</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ohshiro, Taichi</creatorcontrib><creatorcontrib>Rudel, Lawrence L</creatorcontrib><creatorcontrib>Ōmura, Satoshi</creatorcontrib><creatorcontrib>Tomoda, Hiroshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of antibiotics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ohshiro, Taichi</au><au>Rudel, Lawrence L</au><au>Ōmura, Satoshi</au><au>Tomoda, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Selectivity of Microbial Acyl-CoA : cholesterol Acyltransferase Inhibitors toward Isozymes</atitle><jtitle>Journal of antibiotics</jtitle><stitle>J Antibiot</stitle><addtitle>J Antibiot (Tokyo)</addtitle><date>2007-01-01</date><risdate>2007</risdate><volume>60</volume><issue>1</issue><spage>43</spage><epage>51</epage><pages>43-51</pages><issn>0021-8820</issn><eissn>1881-1469</eissn><abstract>The selectivity of microbial inhibitors of acyl-CoA : cholesterol acyltransferase (ACAT) toward the two isozymes, ACAT1 and ACAT2, was assessed in cell-based assays. Purpactin A (IC
50
values of ACAT1
vs
. IC
50
values of ACAT2; 2.5 μM
vs
. 1.5 μM), terpendole C (10 μM
vs
. 10 μM), glisoprenin A (4.3 μM
vs
. 10 μM), spylidone (25 μM
vs
. 5.0 μM) and synthetic CL-283,546 (0.1 μM
vs
. 0.09 μM) inhibited ACAT1 and ACAT2 to similar extents. Beauveriolides I (0.6 μM
vs
. 20 μM) and III (0.9 μM
vs
. >20 μM) inhibited ACAT1 rather selectively, while pyripyropenes A (>80 μM
vs
. 0.07 μM), B (48 μM
vs
. 2.0 μM), C (32 μM
vs
. 0.36 μM) and D (38 μM
vs
. 1.5 μM) showed selective inhibition against ACAT2. In particular, pyripyropene A was found to be the most selective ACAT2 inhibitor with a selective index of more than 1,000.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>17390588</pmid><doi>10.1038/ja.2007.6</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of antibiotics, 2007-01, Vol.60 (1), p.43-51 |
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| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Bacteriology Biomedical and Life Sciences Bioorganic Chemistry CHO Cells Cholesterol Cholesterol Esters - biosynthesis Cricetinae Cricetulus Depsipeptides - pharmacology Diterpenes - pharmacology Enzyme Inhibitors - pharmacology Fatty Alcohols - pharmacology Heterocyclic Compounds, 3-Ring - pharmacology Indoles - pharmacology Isoenzymes - antagonists & inhibitors Life Sciences Macrophages, Peritoneal - drug effects Macrophages, Peritoneal - metabolism Medicinal Chemistry Mice Microbiology Molecular Structure Organic Chemistry original-article Phenanthrenes - pharmacology Phenylurea Compounds - pharmacology Pyridines - pharmacology Sesquiterpenes - pharmacology Spiro Compounds - pharmacology Sterol O-Acyltransferase - antagonists & inhibitors Sterol O-Acyltransferase 2 |
| title | Selectivity of Microbial Acyl-CoA : cholesterol Acyltransferase Inhibitors toward Isozymes |
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