The effects of diminishing albumin binding to some Endothelin receptor antagonists
As a pharmacological class, Endothelin-A receptor (ET A) antagonists are highly bound (> 98%) to serum albumin. In the presence of physiological concentrations of albumin, their affinities for ET A decrease 10 to 100 fold. We have prepared ET A antagonists which exhibit lower degrees of binding t...
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| Veröffentlicht in: | Life sciences (1973) 1998, Vol.63 (21), p.1905-1912 |
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| container_issue | 21 |
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| container_title | Life sciences (1973) |
| container_volume | 63 |
| creator | Szczepankiewicz, Bruce G. Bal, Radhika B. von Geldern, Thomas W. Wu-Wong, Jinshyun R. Chiou, William J. Dixon, Douglas B. Opgenorth, Terry J. Hoffman, Daniel J. Borre, Anthony J. Marsh, Kennan C. Nguyen, Bach N. |
| description | As a pharmacological class, Endothelin-A receptor (ET
A) antagonists are highly bound (> 98%) to serum albumin. In the presence of physiological concentrations of albumin, their affinities for ET
A decrease 10 to 100 fold. We have prepared ET
A antagonists which exhibit lower degrees of binding to albumin, while maintaining potency and selectivity for the ET
A receptor. The protein induced IC
50 shift is reduced or eliminated in this new series of compounds. The compounds also display altered
in vivo and pharmacokinetic profiles which may be consistent with their lower degree of protein binding. |
| doi_str_mv | 10.1016/S0024-3205(98)00466-4 |
| format | Article |
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A) antagonists are highly bound (> 98%) to serum albumin. In the presence of physiological concentrations of albumin, their affinities for ET
A decrease 10 to 100 fold. We have prepared ET
A antagonists which exhibit lower degrees of binding to albumin, while maintaining potency and selectivity for the ET
A receptor. The protein induced IC
50 shift is reduced or eliminated in this new series of compounds. The compounds also display altered
in vivo and pharmacokinetic profiles which may be consistent with their lower degree of protein binding.</description><identifier>ISSN: 0024-3205</identifier><identifier>EISSN: 1879-0631</identifier><identifier>DOI: 10.1016/S0024-3205(98)00466-4</identifier><identifier>PMID: 9825768</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>A-127722 ; A-200379 ; A-207508 ; A-212194 ; albumin binding ; Animals ; Atrasentan ; CHO Cells ; Chromatography, High Pressure Liquid ; Cricetinae ; endothelin ; endothelin receptor ; Endothelin Receptor Antagonists ; Endothelin-1 - metabolism ; Endothelin-3 - metabolism ; endothelin-A receptor antagonist ; Humans ; Male ; plasma protein binding ; Protein Binding ; Pyrrolidines - metabolism ; Pyrrolidines - pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Receptor, Endothelin A ; Receptor, Endothelin B ; Receptors, Endothelin - metabolism ; Serum Albumin - metabolism ; Stereoisomerism</subject><ispartof>Life sciences (1973), 1998, Vol.63 (21), p.1905-1912</ispartof><rights>1998</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c308t-9cea2957c0fddcc94f418349d53380ddc4c3e1eea02c65f2e6cf817ff3a78183</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0024-3205(98)00466-4$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,4025,27928,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9825768$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Szczepankiewicz, Bruce G.</creatorcontrib><creatorcontrib>Bal, Radhika B.</creatorcontrib><creatorcontrib>von Geldern, Thomas W.</creatorcontrib><creatorcontrib>Wu-Wong, Jinshyun R.</creatorcontrib><creatorcontrib>Chiou, William J.</creatorcontrib><creatorcontrib>Dixon, Douglas B.</creatorcontrib><creatorcontrib>Opgenorth, Terry J.</creatorcontrib><creatorcontrib>Hoffman, Daniel J.</creatorcontrib><creatorcontrib>Borre, Anthony J.</creatorcontrib><creatorcontrib>Marsh, Kennan C.</creatorcontrib><creatorcontrib>Nguyen, Bach N.</creatorcontrib><title>The effects of diminishing albumin binding to some Endothelin receptor antagonists</title><title>Life sciences (1973)</title><addtitle>Life Sci</addtitle><description>As a pharmacological class, Endothelin-A receptor (ET
A) antagonists are highly bound (> 98%) to serum albumin. In the presence of physiological concentrations of albumin, their affinities for ET
A decrease 10 to 100 fold. We have prepared ET
A antagonists which exhibit lower degrees of binding to albumin, while maintaining potency and selectivity for the ET
A receptor. The protein induced IC
50 shift is reduced or eliminated in this new series of compounds. The compounds also display altered
in vivo and pharmacokinetic profiles which may be consistent with their lower degree of protein binding.</description><subject>A-127722</subject><subject>A-200379</subject><subject>A-207508</subject><subject>A-212194</subject><subject>albumin binding</subject><subject>Animals</subject><subject>Atrasentan</subject><subject>CHO Cells</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Cricetinae</subject><subject>endothelin</subject><subject>endothelin receptor</subject><subject>Endothelin Receptor Antagonists</subject><subject>Endothelin-1 - metabolism</subject><subject>Endothelin-3 - metabolism</subject><subject>endothelin-A receptor antagonist</subject><subject>Humans</subject><subject>Male</subject><subject>plasma protein binding</subject><subject>Protein Binding</subject><subject>Pyrrolidines - metabolism</subject><subject>Pyrrolidines - pharmacokinetics</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, Endothelin A</subject><subject>Receptor, Endothelin B</subject><subject>Receptors, Endothelin - metabolism</subject><subject>Serum Albumin - metabolism</subject><subject>Stereoisomerism</subject><issn>0024-3205</issn><issn>1879-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkFtLAzEQhYMotVZ_QmGfRB9WJ5u9ZJ9ESr1AQdC-hzSZtJHdTd1kBf-96QVfhYFhcs6ZIR8hUwp3FGh5_wGQ5SnLoLip-S1AXpZpfkLGlFd1CiWjp2T8ZzknF95_AkBRVGxERjXPiqrkY_K-3GCCxqAKPnEm0ba1nfUb260T2ayGOCUr2-ndHFziXYvJvNMubLCJUo8Kt8H1ieyCXLuYDP6SnBnZeLw69glZPs2Xs5d08fb8OntcpIoBD2mtUGZ1USkwWitV5yannOW1LhjjEJ9yxZAiSshUWZgMS2U4rYxhsuLROSHXh7Xb3n0N6INorVfYNLJDN3hRAcTiNBqLg1H1zvsejdj2tpX9j6AgdijFHqXYcRI1F3uUIo-56fHAsGpR_6WO7KL-cNAxfvLbYi-8stgp1DZiCUI7-8-FX3k7hH0</recordid><startdate>1998</startdate><enddate>1998</enddate><creator>Szczepankiewicz, Bruce G.</creator><creator>Bal, Radhika B.</creator><creator>von Geldern, Thomas W.</creator><creator>Wu-Wong, Jinshyun R.</creator><creator>Chiou, William J.</creator><creator>Dixon, Douglas B.</creator><creator>Opgenorth, Terry J.</creator><creator>Hoffman, Daniel J.</creator><creator>Borre, Anthony J.</creator><creator>Marsh, Kennan C.</creator><creator>Nguyen, Bach N.</creator><general>Elsevier Inc</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>1998</creationdate><title>The effects of diminishing albumin binding to some Endothelin receptor antagonists</title><author>Szczepankiewicz, Bruce G. ; Bal, Radhika B. ; von Geldern, Thomas W. ; Wu-Wong, Jinshyun R. ; Chiou, William J. ; Dixon, Douglas B. ; Opgenorth, Terry J. ; Hoffman, Daniel J. ; Borre, Anthony J. ; Marsh, Kennan C. ; Nguyen, Bach N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c308t-9cea2957c0fddcc94f418349d53380ddc4c3e1eea02c65f2e6cf817ff3a78183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>A-127722</topic><topic>A-200379</topic><topic>A-207508</topic><topic>A-212194</topic><topic>albumin binding</topic><topic>Animals</topic><topic>Atrasentan</topic><topic>CHO Cells</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Cricetinae</topic><topic>endothelin</topic><topic>endothelin receptor</topic><topic>Endothelin Receptor Antagonists</topic><topic>Endothelin-1 - metabolism</topic><topic>Endothelin-3 - metabolism</topic><topic>endothelin-A receptor antagonist</topic><topic>Humans</topic><topic>Male</topic><topic>plasma protein binding</topic><topic>Protein Binding</topic><topic>Pyrrolidines - metabolism</topic><topic>Pyrrolidines - pharmacokinetics</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, Endothelin A</topic><topic>Receptor, Endothelin B</topic><topic>Receptors, Endothelin - metabolism</topic><topic>Serum Albumin - metabolism</topic><topic>Stereoisomerism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Szczepankiewicz, Bruce G.</creatorcontrib><creatorcontrib>Bal, Radhika B.</creatorcontrib><creatorcontrib>von Geldern, Thomas W.</creatorcontrib><creatorcontrib>Wu-Wong, Jinshyun R.</creatorcontrib><creatorcontrib>Chiou, William J.</creatorcontrib><creatorcontrib>Dixon, Douglas B.</creatorcontrib><creatorcontrib>Opgenorth, Terry J.</creatorcontrib><creatorcontrib>Hoffman, Daniel J.</creatorcontrib><creatorcontrib>Borre, Anthony J.</creatorcontrib><creatorcontrib>Marsh, Kennan C.</creatorcontrib><creatorcontrib>Nguyen, Bach N.</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>Life sciences (1973)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Szczepankiewicz, Bruce G.</au><au>Bal, Radhika B.</au><au>von Geldern, Thomas W.</au><au>Wu-Wong, Jinshyun R.</au><au>Chiou, William J.</au><au>Dixon, Douglas B.</au><au>Opgenorth, Terry J.</au><au>Hoffman, Daniel J.</au><au>Borre, Anthony J.</au><au>Marsh, Kennan C.</au><au>Nguyen, Bach N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effects of diminishing albumin binding to some Endothelin receptor antagonists</atitle><jtitle>Life sciences (1973)</jtitle><addtitle>Life Sci</addtitle><date>1998</date><risdate>1998</risdate><volume>63</volume><issue>21</issue><spage>1905</spage><epage>1912</epage><pages>1905-1912</pages><issn>0024-3205</issn><eissn>1879-0631</eissn><abstract>As a pharmacological class, Endothelin-A receptor (ET
A) antagonists are highly bound (> 98%) to serum albumin. In the presence of physiological concentrations of albumin, their affinities for ET
A decrease 10 to 100 fold. We have prepared ET
A antagonists which exhibit lower degrees of binding to albumin, while maintaining potency and selectivity for the ET
A receptor. The protein induced IC
50 shift is reduced or eliminated in this new series of compounds. The compounds also display altered
in vivo and pharmacokinetic profiles which may be consistent with their lower degree of protein binding.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>9825768</pmid><doi>10.1016/S0024-3205(98)00466-4</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Life sciences (1973), 1998, Vol.63 (21), p.1905-1912 |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | A-127722 A-200379 A-207508 A-212194 albumin binding Animals Atrasentan CHO Cells Chromatography, High Pressure Liquid Cricetinae endothelin endothelin receptor Endothelin Receptor Antagonists Endothelin-1 - metabolism Endothelin-3 - metabolism endothelin-A receptor antagonist Humans Male plasma protein binding Protein Binding Pyrrolidines - metabolism Pyrrolidines - pharmacokinetics Rats Rats, Sprague-Dawley Receptor, Endothelin A Receptor, Endothelin B Receptors, Endothelin - metabolism Serum Albumin - metabolism Stereoisomerism |
| title | The effects of diminishing albumin binding to some Endothelin receptor antagonists |
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