{"id":"https://openalex.org/W1984246155","doi":"https://doi.org/10.1158/0008-5472.can-03-3344","title":"Imatinib Mesylate Is a Potent Inhibitor of the ABCG2 (BCRP) Transporter and Reverses Resistance to Topotecan and SN-38 in Vitro","display_name":"Imatinib Mesylate Is a Potent Inhibitor of the ABCG2 (BCRP) Transporter and Reverses Resistance to Topotecan and SN-38 in Vitro","publication_year":2004,"publication_date":"2004-04-01","ids":{"openalex":"https://openalex.org/W1984246155","doi":"https://doi.org/10.1158/0008-5472.can-03-3344","mag":"1984246155","pmid":"https://pubmed.ncbi.nlm.nih.gov/15059881"},"language":"en","primary_location":{"id":"doi:10.1158/0008-5472.can-03-3344","doi":"https://doi.org/10.1158/0008-5472.can-03-3344","is_oa":false,"landing_page_url":"https://doi.org/10.1158/0008-5472.can-03-3344","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"},"volume":null,"type":"article","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/A5109173471","display_name":"Peter J. Houghton","orcid":"https://orcid.org/0000-0002-2400-8184","observed_orcids":["https://orcid.org/0000-0002-2400-8184"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Peter J. Houghton","raw_affiliation_strings":["1Molecular Pharmacology and Departments of"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Molecular Pharmacology and Departments of","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111727293","display_name":"Glen S. Germain","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Glen S. Germain","raw_affiliation_strings":["1Molecular Pharmacology and Departments of"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Molecular Pharmacology and Departments of","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5033300554","display_name":"Franklin C. Harwood","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Franklin C. Harwood","raw_affiliation_strings":["1Molecular Pharmacology and Departments of"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Molecular Pharmacology and Departments of","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5053239538","display_name":"John D. Schuetz","orcid":"https://orcid.org/0000-0003-0779-1303","observed_orcids":["https://orcid.org/0000-0003-0779-1303"]},"institutions":[{"id":"https://openalex.org/I1313298211","display_name":"St. Jude Children's Research Hospital","ror":"https://ror.org/02r3e0967","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1313298211","https://openalex.org/I2802152183"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"John D. Schuetz","raw_affiliation_strings":["2Pharmaceutical Sciences, St. Jude Children\u2019s Research Hospital, Memphis, Tennessee, and"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Pharmaceutical Sciences, St. Jude Children\u2019s Research Hospital, Memphis, Tennessee, and","institution_ids":["https://openalex.org/I1313298211"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5043293908","display_name":"Clinton F. Stewart","orcid":"https://orcid.org/0000-0002-1546-9720","observed_orcids":["https://orcid.org/0000-0002-1546-9720"]},"institutions":[{"id":"https://openalex.org/I1313298211","display_name":"St. Jude Children's Research Hospital","ror":"https://ror.org/02r3e0967","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1313298211","https://openalex.org/I2802152183"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Clinton F. Stewart","raw_affiliation_strings":["2Pharmaceutical Sciences, St. Jude Children\u2019s Research Hospital, Memphis, Tennessee, and"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Pharmaceutical Sciences, St. Jude Children\u2019s Research Hospital, Memphis, Tennessee, and","institution_ids":["https://openalex.org/I1313298211"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5083068452","display_name":"Elisabeth Buchdunger","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1283582996","display_name":"Novartis (Switzerland)","ror":"https://ror.org/02f9zrr09","country_code":"CH","type":"company","lineage":["https://openalex.org/I1283582996"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Elisabeth Buchdunger","raw_affiliation_strings":["3Novartis Pharma AG, Basel, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"3Novartis Pharma AG, Basel, Switzerland","institution_ids":["https://openalex.org/I1283582996"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5043955000","display_name":"Peter M. Traxler","orcid":"https://orcid.org/0000-0003-0373-8839","observed_orcids":["https://orcid.org/0000-0003-0373-8839"]},"institutions":[{"id":"https://openalex.org/I1283582996","display_name":"Novartis (Switzerland)","ror":"https://ror.org/02f9zrr09","country_code":"CH","type":"company","lineage":["https://openalex.org/I1283582996"]}],"countries":["CH"],"is_corresponding":false,"raw_author_name":"Peter Traxler","raw_affiliation_strings":["3Novartis Pharma AG, Basel, Switzerland"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"3Novartis Pharma AG, Basel, Switzerland","institution_ids":["https://openalex.org/I1283582996"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":14.7055,"has_fulltext":false,"cited_by_count":322,"citation_normalized_percentile":{"value":0.99498085,"is_in_top_1_percent":true,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":97,"max":100},"biblio":{"volume":"64","issue":"7","first_page":"2333","last_page":"2337"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10570","display_name":"Drug Transport and Resistance Mechanisms","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10570","display_name":"Drug Transport and Resistance Mechanisms","score":1.0,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11845","display_name":"Cancer therapeutics and mechanisms","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.0,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/imatinib-mesylate","display_name":"imatinib mesylate","score":0.9990000128746033},{"id":"https://openalex.org/keywords/abcg2","display_name":"ABCG2","score":0.9900000095367432},{"id":"https://openalex.org/keywords/topotecan-resistance","display_name":"topotecan resistance","score":0.8220000267028809},{"id":"https://openalex.org/keywords/sn-38","display_name":"SN-38","score":0.8640000224113464},{"id":"https://openalex.org/keywords/camptothecin-derivatives","display_name":"camptothecin derivatives","score":0.8410000205039978},{"id":"https://openalex.org/keywords/multidrug-resistance-reversal","display_name":"multidrug resistance reversal","score":0.7979999780654907},{"id":"https://openalex.org/keywords/drug-efflux","display_name":"drug efflux","score":0.625},{"id":"https://openalex.org/keywords/tyrosine-kinase-inhibitors","display_name":"tyrosine kinase inhibitors","score":0.8119999766349792},{"id":"https://openalex.org/keywords/drug-accumulation","display_name":"drug accumulation","score":0.45100000500679016},{"id":"https://openalex.org/keywords/atp-depletion","display_name":"ATP depletion","score":0.5090000033378601}],"concepts":[{"id":"https://openalex.org/C3019892230","wikidata":"https://www.wikidata.org/wiki/Q177094","display_name":"Imatinib mesylate","level":4,"score":0.9095224738121033},{"id":"https://openalex.org/C512196","wikidata":"https://www.wikidata.org/wiki/Q4650095","display_name":"Abcg2","level":5,"score":0.8638045787811279},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.7433072328567505},{"id":"https://openalex.org/C2778820342","wikidata":"https://www.wikidata.org/wiki/Q906415","display_name":"Tyrosine-kinase inhibitor","level":3,"score":0.6069803833961487},{"id":"https://openalex.org/C2781209748","wikidata":"https://www.wikidata.org/wiki/Q419953","display_name":"Topotecan","level":3,"score":0.5985305905342102},{"id":"https://openalex.org/C2780194963","wikidata":"https://www.wikidata.org/wiki/Q903441","display_name":"Mesylate","level":2,"score":0.5725659132003784},{"id":"https://openalex.org/C42362537","wikidata":"https://www.wikidata.org/wiki/Q87099740","display_name":"Tyrosine kinase","level":3,"score":0.5649155378341675},{"id":"https://openalex.org/C2777583451","wikidata":"https://www.wikidata.org/wiki/Q177094","display_name":"Imatinib","level":3,"score":0.5218811631202698},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5030311942100525},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.310377299785614},{"id":"https://openalex.org/C44312359","wikidata":"https://www.wikidata.org/wiki/Q286958","display_name":"ATP-binding cassette transporter","level":4,"score":0.2984192967414856},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.29662442207336426},{"id":"https://openalex.org/C149011108","wikidata":"https://www.wikidata.org/wiki/Q652985","display_name":"Transporter","level":3,"score":0.2894911766052246},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.15748855471611023},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.14196553826332092},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.13484856486320496},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.0993226170539856},{"id":"https://openalex.org/C2776694085","wikidata":"https://www.wikidata.org/wiki/Q974135","display_name":"Chemotherapy","level":2,"score":0.06139254570007324},{"id":"https://openalex.org/C2778729363","wikidata":"https://www.wikidata.org/wiki/Q11688946","display_name":"Myeloid leukemia","level":2,"score":0.0},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000068877","descriptor_name":"Imatinib Mesylate","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000070997","descriptor_name":"ATP Binding Cassette Transporter, Subfamily G, Member 2","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000077146","descriptor_name":"Irinotecan","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D001549","descriptor_name":"Benzamides","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001859","descriptor_name":"Bone Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D001859","descriptor_name":"Bone Neoplasms","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D002166","descriptor_name":"Camptothecin","qualifier_ui":"Q000031","qualifier_name":"analogs & derivatives","is_major_topic":false},{"descriptor_ui":"D002166","descriptor_name":"Camptothecin","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D004791","descriptor_name":"Enzyme Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009363","descriptor_name":"Neoplasm Proteins","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D010879","descriptor_name":"Piperazines","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D011743","descriptor_name":"Pyrimidines","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D012516","descriptor_name":"Osteosarcoma","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D012516","descriptor_name":"Osteosarcoma","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D018528","descriptor_name":"ATP-Binding Cassette Transporters","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D019008","descriptor_name":"Drug Resistance, Neoplasm","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019772","descriptor_name":"Topotecan","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D019772","descriptor_name":"Topotecan","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D045744","descriptor_name":"Cell Line, Tumor","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1158/0008-5472.can-03-3344","doi":"https://doi.org/10.1158/0008-5472.can-03-3344","is_oa":false,"landing_page_url":"https://doi.org/10.1158/0008-5472.can-03-3344","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"},{"id":"pmid:15059881","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/15059881","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":"Cancer research","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":0.98580002784729}],"study_designs":[],"awards":[{"id":"https://openalex.org/G1292651958","display_name":"MTOR as a Therapeutic Target in Childhood Cancer","funder_award_id":"R01CA096696","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G5145123177","display_name":"Studies of Childhood Solid Tumors","funder_award_id":"P01CA023099","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G707951704","display_name":null,"funder_award_id":"CA7776","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G9000904664","display_name":"Cancer Center Support Grant (CCSG)","funder_award_id":"P30CA021765","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":11,"referenced_works":["https://openalex.org/W1965456986","https://openalex.org/W2014593961","https://openalex.org/W2098560357","https://openalex.org/W2101027166","https://openalex.org/W2126358767","https://openalex.org/W2126376257","https://openalex.org/W2140513230","https://openalex.org/W2142024216","https://openalex.org/W2151504205","https://openalex.org/W2168471377","https://openalex.org/W2329648702"],"related_works":["https://openalex.org/W1967859455","https://openalex.org/W2121587436","https://openalex.org/W2149758605","https://openalex.org/W2129342281","https://openalex.org/W2513944931","https://openalex.org/W2171223909","https://openalex.org/W2027128842","https://openalex.org/W2003596377","https://openalex.org/W2556113557","https://openalex.org/W2019346113"],"abstract_inverted_index":{"Imatinib":[0,21],"mesylate":[1,93,131,148],"(Gleevec,":[2],"STI571)":[3],"is":[4,155],"a":[5,157],"kinase":[6,28],"inhibitor":[7],"selective":[8],"for":[9,39,74,159],"Bcr-Abl,":[10],"activated":[11],"c-Kit":[12],"kinases,":[13],"and":[14,66,100,102,127,136],"platelet-derived":[15],"growth":[16],"factor":[17],"receptor":[18],"tyrosine":[19,27],"kinase.":[20],"mesylate,":[22,83],"similar":[23],"to":[24,48,62,71,98,122],"many":[25],"other":[26],"inhibitors":[29],"(TKIs),":[30],"such":[31],"as":[32],"members":[33],"of":[34,52,78,106,116,129,152],"the":[35,50,53,69,75,150],"4-anilinoquinazoline":[36,43],"class,":[37],"competes":[38],"ATP":[40,141],"binding.":[41],"Previously,":[42],"TKIs":[44],"have":[45],"been":[46,86],"shown":[47],"inhibit":[49,72],"function":[51,151],"breast":[54],"cancer":[55],"resistance-associated":[56],"drug":[57],"transporter":[58],"(ABCG2),":[59],"reversing":[60],"resistance":[61,97,121],"camptothecin":[63],"derivatives":[64],"topotecan":[65,99,107],"SN-38.":[67],"However,":[68,114],"potential":[70],"ABCG2":[73,117,153],"2-phenylamino-pyrimidine":[76],"class":[77],"TKIs,":[79],"exemplified":[80],"by":[81,140],"imatinib":[82,92,123,147],"has":[84],"not":[85,119,156],"examined.":[87],"Here,":[88],"we":[89],"show":[90],"that":[91,146],"potently":[94],"reverses":[95],"ABCG2-mediated":[96],"SN-38":[101],"significantly":[103],"increases":[104],"accumulation":[105,126],"only":[108],"in":[109],"cells":[110,138],"expressing":[111],"functional":[112],"ABCG2.":[113],"overexpression":[115],"does":[118],"confer":[120],"mesylate.":[124],"Furthermore,":[125],"efflux":[128],"[(14)C]imatinib":[130],"are":[132],"unaltered":[133],"between":[134],"ABCG2-expressing":[135],"non-ABCG2-expressing":[137],"or":[139],"depletion.":[142],"These":[143],"results":[144],"suggest":[145],"inhibits":[149],"but":[154],"substrate":[158],"this":[160],"transporter.":[161]},"counts_by_year":[{"year":2026,"cited_by_count":4},{"year":2025,"cited_by_count":6},{"year":2024,"cited_by_count":5},{"year":2023,"cited_by_count":9},{"year":2022,"cited_by_count":6},{"year":2021,"cited_by_count":9},{"year":2020,"cited_by_count":10},{"year":2019,"cited_by_count":8},{"year":2018,"cited_by_count":8},{"year":2017,"cited_by_count":10},{"year":2016,"cited_by_count":6},{"year":2015,"cited_by_count":9},{"year":2014,"cited_by_count":20},{"year":2013,"cited_by_count":20},{"year":2012,"cited_by_count":23}],"updated_date":"2026-11-06T12:05:46.655746","created_date":"2016-06-24T00:00:00"}