{"id":"https://openalex.org/W2015415371","doi":"https://doi.org/10.1021/tx0341409","title":"In Vitro Metabolism of 2-Acetylbenzothiophene: Relevance to Zileuton Hepatotoxicity","display_name":"In Vitro Metabolism of 2-Acetylbenzothiophene: Relevance to Zileuton Hepatotoxicity","publication_year":2004,"publication_date":"2004-01-24","ids":{"openalex":"https://openalex.org/W2015415371","doi":"https://doi.org/10.1021/tx0341409","mag":"2015415371","pmid":"https://pubmed.ncbi.nlm.nih.gov/14967000"},"language":"en","primary_location":{"id":"doi:10.1021/tx0341409","doi":"https://doi.org/10.1021/tx0341409","is_oa":false,"landing_page_url":"https://doi.org/10.1021/tx0341409","pdf_url":null,"source":{"id":"https://openalex.org/S152840809","display_name":"Chemical Research in Toxicology","issn_l":"0893-228X","issn":["0893-228X","1520-5010"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Chemical Research in Toxicology","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5027719975","display_name":"Elizabeth Joshi","orcid":"https://orcid.org/0000-0003-3267-0634","observed_orcids":["https://orcid.org/0000-0003-3267-0634"]},"institutions":[{"id":"https://openalex.org/I51556381","display_name":"University of Virginia","ror":"https://ror.org/0153tk833","country_code":"US","type":"education","lineage":["https://openalex.org/I51556381"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Elizabeth M. Joshi","raw_affiliation_strings":["Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901","Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901","institution_ids":["https://openalex.org/I51556381"]},{"raw_affiliation_string":"Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901, USA","institution_ids":["https://openalex.org/I51556381"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5085870272","display_name":"Brian H. Heasley","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I51556381","display_name":"University of Virginia","ror":"https://ror.org/0153tk833","country_code":"US","type":"education","lineage":["https://openalex.org/I51556381"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Brian H. Heasley","raw_affiliation_strings":["Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901","institution_ids":["https://openalex.org/I51556381"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5068275315","display_name":"Mahendra D. Chordia","orcid":"https://orcid.org/0000-0001-9364-4697","observed_orcids":["https://orcid.org/0000-0001-9364-4697"]},"institutions":[{"id":"https://openalex.org/I51556381","display_name":"University of Virginia","ror":"https://ror.org/0153tk833","country_code":"US","type":"education","lineage":["https://openalex.org/I51556381"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mahendra D. Chordia","raw_affiliation_strings":["Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901","institution_ids":["https://openalex.org/I51556381"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5111708048","display_name":"Timothy L. Macdonald","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I51556381","display_name":"University of Virginia","ror":"https://ror.org/0153tk833","country_code":"US","type":"education","lineage":["https://openalex.org/I51556381"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Timothy L. Macdonald","raw_affiliation_strings":["Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901","institution_ids":["https://openalex.org/I51556381"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I51556381"],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":2.1225,"has_fulltext":false,"cited_by_count":84,"citation_normalized_percentile":{"value":0.84951274,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":99},"biblio":{"volume":"17","issue":"2","first_page":"137","last_page":"143"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11465","display_name":"Drug-Induced Hepatotoxicity and Protection","score":0.9648000001907349,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11465","display_name":"Drug-Induced Hepatotoxicity and Protection","score":0.9648000001907349,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.032600000500679016,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12356","display_name":"Bioactive Compounds and Antitumor Agents","score":0.0007999999797903001,"subfield":{"id":"https://openalex.org/subfields/3005","display_name":"Toxicology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/zileuton","display_name":"zileuton","score":0.9950000047683716},{"id":"https://openalex.org/keywords/hepatotoxicity","display_name":"hepatotoxicity","score":0.8930000066757202},{"id":"https://openalex.org/keywords/drug-metabolism","display_name":"drug metabolism","score":0.7080000042915344},{"id":"https://openalex.org/keywords/5-lipoxygenase-inhibitors","display_name":"5-lipoxygenase inhibitors","score":0.7789999842643738},{"id":"https://openalex.org/keywords/leukotriene-pathway","display_name":"leukotriene pathway","score":0.7799999713897705},{"id":"https://openalex.org/keywords/s-oxides","display_name":"S-oxides","score":0.4830000102519989},{"id":"https://openalex.org/keywords/glutathione-adducts","display_name":"glutathione adducts","score":0.824999988079071},{"id":"https://openalex.org/keywords/n-acetylcysteine","display_name":"N-acetylcysteine","score":0.8899999856948853},{"id":"https://openalex.org/keywords/reactive-metabolites","display_name":"reactive metabolites","score":0.6069999933242798},{"id":"https://openalex.org/keywords/metabolic-activation","display_name":"metabolic activation","score":0.6359999775886536},{"id":"https://openalex.org/keywords/human-liver-microsomes","display_name":"human liver microsomes","score":0.7720000147819519},{"id":"https://openalex.org/keywords/cytotoxicity","display_name":"cytotoxicity","score":0.7570000290870667}],"concepts":[{"id":"https://openalex.org/C2781370401","wikidata":"https://www.wikidata.org/wiki/Q202998","display_name":"Zileuton","level":5,"score":0.8802709579467773},{"id":"https://openalex.org/C2777477808","wikidata":"https://www.wikidata.org/wiki/Q407595","display_name":"Metabolite","level":2,"score":0.807133674621582},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7204437255859375},{"id":"https://openalex.org/C108204754","wikidata":"https://www.wikidata.org/wiki/Q353392","display_name":"Adduct","level":2,"score":0.6833144426345825},{"id":"https://openalex.org/C538909803","wikidata":"https://www.wikidata.org/wiki/Q116907","display_name":"Glutathione","level":3,"score":0.6601939797401428},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.6284289956092834},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.5217112898826599},{"id":"https://openalex.org/C87644729","wikidata":"https://www.wikidata.org/wiki/Q547502","display_name":"Microsome","level":3,"score":0.5087681412696838},{"id":"https://openalex.org/C2780539824","wikidata":"https://www.wikidata.org/wiki/Q1798974","display_name":"Mercapturic acid","level":4,"score":0.49370893836021423},{"id":"https://openalex.org/C29730261","wikidata":"https://www.wikidata.org/wiki/Q274160","display_name":"Toxicity","level":2,"score":0.47277238965034485},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.46303069591522217},{"id":"https://openalex.org/C62231903","wikidata":"https://www.wikidata.org/wiki/Q1057","display_name":"Metabolism","level":2,"score":0.4549427330493927},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.4407760202884674},{"id":"https://openalex.org/C2779907587","wikidata":"https://www.wikidata.org/wiki/Q14901439","display_name":"Glucuronidation","level":4,"score":0.4301171898841858},{"id":"https://openalex.org/C114246631","wikidata":"https://www.wikidata.org/wiki/Q187661","display_name":"Carcinogen","level":2,"score":0.42963290214538574},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.34439435601234436},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.2569374442100525},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.14789950847625732},{"id":"https://openalex.org/C90342290","wikidata":"https://www.wikidata.org/wiki/Q94234745","display_name":"Arachidonate 5-lipoxygenase","level":4,"score":0.14245927333831787},{"id":"https://openalex.org/C2778078955","wikidata":"https://www.wikidata.org/wiki/Q407699","display_name":"Arachidonic acid","level":3,"score":0.13151228427886963},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.10774043202400208},{"id":"https://openalex.org/C150903083","wikidata":"https://www.wikidata.org/wiki/Q7108","display_name":"Biotechnology","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002460","descriptor_name":"Cell Line","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005978","descriptor_name":"Glutathione","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D006207","descriptor_name":"Half-Life","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006918","descriptor_name":"Hydroxyurea","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":true},{"descriptor_ui":"D006918","descriptor_name":"Hydroxyurea","qualifier_ui":"Q000633","qualifier_name":"toxicity","is_major_topic":true},{"descriptor_ui":"D008099","descriptor_name":"Liver","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true},{"descriptor_ui":"D009682","descriptor_name":"Magnetic Resonance Spectroscopy","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013876","descriptor_name":"Thiophenes","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D013876","descriptor_name":"Thiophenes","qualifier_ui":"Q000633","qualifier_name":"toxicity","is_major_topic":false},{"descriptor_ui":"D021241","descriptor_name":"Spectrometry, Mass, Electrospray Ionization","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051381","descriptor_name":"Rats","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/tx0341409","doi":"https://doi.org/10.1021/tx0341409","is_oa":false,"landing_page_url":"https://doi.org/10.1021/tx0341409","pdf_url":null,"source":{"id":"https://openalex.org/S152840809","display_name":"Chemical Research in Toxicology","issn_l":"0893-228X","issn":["0893-228X","1520-5010"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Chemical Research in Toxicology","raw_type":"journal-article"},{"id":"pmid:14967000","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/14967000","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Chemical research in toxicology","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9391000270843506}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":6,"referenced_works":["https://openalex.org/W1982620166","https://openalex.org/W2017120903","https://openalex.org/W2018683888","https://openalex.org/W2029251290","https://openalex.org/W2031871466","https://openalex.org/W2079421115"],"related_works":["https://openalex.org/W2129817954","https://openalex.org/W1877562548","https://openalex.org/W7095655936","https://openalex.org/W3011158576","https://openalex.org/W2132311212","https://openalex.org/W1971488707","https://openalex.org/W4205969940","https://openalex.org/W2359516495","https://openalex.org/W2121143255","https://openalex.org/W2163360636"],"abstract_inverted_index":{"Zileuton,":[0],"an":[1],"inhibitor":[2],"of":[3,46,90,103,111,200,208,223,240],"5-lipooxygenase,":[4],"the":[5,9,39,65,88,109,151,158,169,194,198,201,238],"initial":[6],"enzyme":[7],"in":[8,76,108,130,174,226,229,232],"leukotriene":[10],"pathway,":[11],"was":[12],"marketed":[13],"as":[14],"a":[15,44,58,77,139,184,221,249],"new":[16,140],"treatment":[17],"for":[18],"asthma.":[19],"This":[20],"drug":[21],"has":[22,29],"been":[23],"associated":[24],"with":[25,64,85,163,193,215],"liver":[26,40,81],"toxicity,":[27],"which":[28,52],"limited":[30],"its":[31,245],"clinical":[32],"usefulness.":[33],"We":[34],"provide":[35],"evidence":[36],"here":[37,236],"that":[38,72,146,157,218],"toxicity":[41],"likely":[42],"involves":[43],"sequence":[45],"biotransformations":[47],"leading":[48],"to":[49,56,127,137,150,167,182,248],"2-acetylbenzothiophene":[50],"(2-ABT),":[51],"is":[53,74,220],"subsequently":[54],"metabolized":[55],"give":[57],"reactive":[59],"intermediate(s).":[60],"In":[61],"vitro":[62,230],"experiments":[63,192],"human":[66],"lymphoblast":[67],"MCL5":[68],"cell":[69],"line":[70],"demonstrated":[71,145],"2-ABT":[73,86,241],"cytotoxic":[75],"P450-dependent":[78],"manner.":[79],"Human":[80],"microsome":[82],"(HLM)":[83],"incubations":[84],"revealed":[87],"formation":[89,239],"two":[91],"short-lived":[92],"oxidized":[93,116,171],"species,":[94],"\"M":[95,99],"+":[96,100,118,153],"16\"":[97],"and":[98,133,156,165,231,244],"32\".":[101],"Both":[102],"these":[104],"metabolites":[105],"formed":[106,225],"adducts":[107,172,178],"presence":[110],"GSH":[112,123,164],"or":[113,124,188],"NAC.":[114],"Singly":[115],"M":[117,152],"16":[119,154],"adducts,":[120],"from":[121,212,242],"either":[122],"NAC,":[125],"appeared":[126],"be":[128],"unstable":[129],"acidic":[131],"medium":[132],"eliminated":[134,180,202],"water":[135,181],"readily":[136,179],"form":[138,183],"compound.":[141],"Authentic":[142],"synthetic":[143,195],"standards":[144],"2-ABT-S-oxide":[147],"M1":[148],"corresponded":[149],"metabolite":[155,222],"S-oxide":[159,177],"underwent":[160],"nucleophilic":[161],"addition":[162],"NAC":[166],"produce":[168],"singly":[170],"observed":[173],"HLM.":[175],"The":[176,228],"rearomatized":[185],"2-ABT-GSH":[186],"adduct":[187,204],"2-ABT-NAC":[189,203],"adduct.":[190],"Coelution":[191],"standard":[196],"confirmed":[197],"structure":[199],"C1.":[205],"LC/MS":[206],"analyses":[207],"urine":[209],"samples":[210],"collected":[211],"rats":[213],"dosed":[214],"zileuton":[216,224,243],"indicate":[217],"C1":[219],"vivo.":[227],"vivo":[233],"data":[234],"presented":[235],"demonstrate":[237],"further":[246],"bioactivation":[247],"potentially":[250],"toxic":[251],"metabolite.":[252]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":6},{"year":2024,"cited_by_count":2},{"year":2023,"cited_by_count":4},{"year":2022,"cited_by_count":4},{"year":2021,"cited_by_count":4},{"year":2020,"cited_by_count":4},{"year":2019,"cited_by_count":4},{"year":2018,"cited_by_count":2},{"year":2017,"cited_by_count":7},{"year":2016,"cited_by_count":1},{"year":2015,"cited_by_count":4},{"year":2014,"cited_by_count":2},{"year":2013,"cited_by_count":3},{"year":2012,"cited_by_count":8}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}
