{"id":"https://openalex.org/W2979654295","doi":"https://doi.org/10.1182/blood.v118.21.3492.3492","title":"Resistance to Selective FLT3 Inhibitors, Driven by FLT3 Ligand and FLT3 Point Mutations, Can Be Overcome with the Dual FLT3-Aurora Kinase Inhibitor CCT241736,","display_name":"Resistance to Selective FLT3 Inhibitors, Driven by FLT3 Ligand and FLT3 Point Mutations, Can Be Overcome with the Dual FLT3-Aurora Kinase Inhibitor CCT241736,","publication_year":2011,"publication_date":"2011-11-18","ids":{"openalex":"https://openalex.org/W2979654295","doi":"https://doi.org/10.1182/blood.v118.21.3492.3492","mag":"2979654295"},"language":"en","primary_location":{"id":"doi:10.1182/blood.v118.21.3492.3492","doi":"https://doi.org/10.1182/blood.v118.21.3492.3492","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v118.21.3492.3492","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"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/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref"],"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/A5035808651","display_name":"Andrew S. Moore","orcid":"https://orcid.org/0000-0001-8062-1779","observed_orcids":["https://orcid.org/0000-0001-8062-1779"]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Andrew S. Moore","raw_affiliation_strings":["Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5087031667","display_name":"Amir Faisal","orcid":"https://orcid.org/0000-0002-7376-8286","observed_orcids":["https://orcid.org/0000-0002-7376-8286"]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Amir Faisal","raw_affiliation_strings":["Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036587927","display_name":"Vassilios Bavetsias","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Vassilios Bavetsias","raw_affiliation_strings":["Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5102992861","display_name":"David Gonz\u00e1lez de Castro","orcid":"https://orcid.org/0000-0003-0580-5636","observed_orcids":["https://orcid.org/0000-0003-0580-5636"]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"David Gonzalez de Castro","raw_affiliation_strings":["Division of Molecular Pathology, The Institute of Cancer Research, Sutton, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Molecular Pathology, The Institute of Cancer Research, Sutton, United Kingdom","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5008308657","display_name":"Chongbo Sun","orcid":"https://orcid.org/0009-0006-1040-7682","observed_orcids":["https://orcid.org/0009-0006-1040-7682"]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Chongbo Sun","raw_affiliation_strings":["Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5050713768","display_name":"Butrus Atrash","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Butrus Atrash","raw_affiliation_strings":["Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5089603827","display_name":"Melanie R. Valenti","orcid":"https://orcid.org/0000-0001-7610-1375","observed_orcids":["https://orcid.org/0000-0001-7610-1375"]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Melanie Valenti","raw_affiliation_strings":["Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5112904367","display_name":"Alexis de Haven Brandon","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Alexis de Haven Brandon","raw_affiliation_strings":["Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5055603007","display_name":"Sian Avery","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Sian Avery","raw_affiliation_strings":["Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5052706160","display_name":"Andrew D.J. Pearson","orcid":"https://orcid.org/0000-0002-8738-5913","observed_orcids":["https://orcid.org/0000-0002-8738-5913"]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Andrew DJ Pearson","raw_affiliation_strings":["Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003965204","display_name":"Paul Workman","orcid":"https://orcid.org/0000-0003-1659-3034","observed_orcids":["https://orcid.org/0000-0003-1659-3034"]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Paul Workman","raw_affiliation_strings":["Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5055979646","display_name":"Julian Blagg","orcid":"https://orcid.org/0000-0002-7409-0323","observed_orcids":["https://orcid.org/0000-0002-7409-0323"]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Julian Blagg","raw_affiliation_strings":["Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5058014829","display_name":"Florence I. Raynaud","orcid":"https://orcid.org/0000-0003-0957-6279","observed_orcids":["https://orcid.org/0000-0003-0957-6279"]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Florence I Raynaud","raw_affiliation_strings":["Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110523635","display_name":"Suzanne A. Eccles","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Suzanne A Eccles","raw_affiliation_strings":["Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,","institution_ids":["https://openalex.org/I142947616"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5052675504","display_name":"Spiros Linardopoulos","orcid":"https://orcid.org/0000-0002-6600-400X","observed_orcids":["https://orcid.org/0000-0002-6600-400X"]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Spiros Linardopoulos","raw_affiliation_strings":["Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Cancer Therapeutics, The Institute of Cancer Research, Sutton, United Kingdom,","institution_ids":["https://openalex.org/I142947616"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5003965204","https://openalex.org/A5008308657","https://openalex.org/A5036587927","https://openalex.org/A5050713768","https://openalex.org/A5052675504","https://openalex.org/A5052706160","https://openalex.org/A5055603007","https://openalex.org/A5055979646","https://openalex.org/A5058014829","https://openalex.org/A5087031667","https://openalex.org/A5089603827","https://openalex.org/A5102992861","https://openalex.org/A5110523635","https://openalex.org/A5112904367"],"corresponding_institution_ids":["https://openalex.org/I142947616"],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":0.2168,"has_fulltext":false,"cited_by_count":3,"citation_normalized_percentile":{"value":0.65463582,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":96},"biblio":{"volume":"118","issue":"21","first_page":"3492","last_page":"3492"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10309","display_name":"Acute Myeloid Leukemia Research","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"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/T10309","display_name":"Acute Myeloid Leukemia Research","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"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/T11559","display_name":"Retinoids in leukemia and cellular processes","score":9.999999747378752e-05,"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/T11215","display_name":"Chronic Myeloid Leukemia Treatments","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/flt3-itd-mutation","display_name":"FLT3-ITD","score":0.6700000166893005},{"id":"https://openalex.org/keywords/flt3-tkd-mutation","display_name":"FLT3-TKD mutation","score":0.8569999933242798},{"id":"https://openalex.org/keywords/flt3-ligand","display_name":"Flt3 ligand","score":0.8349999785423279},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"drug resistance","score":0.6990000009536743},{"id":"https://openalex.org/keywords/acute-myeloid-leukemia","display_name":"acute myeloid leukemia","score":0.8740000128746033},{"id":"https://openalex.org/keywords/sorafenib","display_name":"sorafenib","score":0.7429999709129333},{"id":"https://openalex.org/keywords/ac220","display_name":"AC220","score":0.9580000042915344},{"id":"https://openalex.org/keywords/aurora-a-kinase","display_name":"AURKA","score":0.4690000116825104},{"id":"https://openalex.org/keywords/aurora-b-kinase","display_name":"Aurora B kinase","score":0.9929999709129333},{"id":"https://openalex.org/keywords/survivin","display_name":"survivin","score":0.675000011920929},{"id":"https://openalex.org/keywords/molm-13","display_name":"MOLM-13","score":0.7559999823570251}],"concepts":[{"id":"https://openalex.org/C2910954276","wikidata":"https://www.wikidata.org/wiki/Q14912399","display_name":"Fms-Like Tyrosine Kinase 3","level":4,"score":0.6627197265625},{"id":"https://openalex.org/C2780808130","wikidata":"https://www.wikidata.org/wiki/Q24745285","display_name":"Aurora kinase","level":4,"score":0.5857198238372803},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5827505588531494},{"id":"https://openalex.org/C176944494","wikidata":"https://www.wikidata.org/wiki/Q1415380","display_name":"Point mutation","level":4,"score":0.5602766275405884},{"id":"https://openalex.org/C2775975398","wikidata":"https://www.wikidata.org/wiki/Q906904","display_name":"Survivin","level":3,"score":0.526484489440918},{"id":"https://openalex.org/C2778695046","wikidata":"https://www.wikidata.org/wiki/Q421136","display_name":"Sorafenib","level":3,"score":0.46195435523986816},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.45984187722206116},{"id":"https://openalex.org/C2778729363","wikidata":"https://www.wikidata.org/wiki/Q11688946","display_name":"Myeloid leukemia","level":2,"score":0.45753175020217896},{"id":"https://openalex.org/C20552341","wikidata":"https://www.wikidata.org/wiki/Q4822632","display_name":"Aurora inhibitor","level":4,"score":0.4305974245071411},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.42486822605133057},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.4225218594074249},{"id":"https://openalex.org/C29537977","wikidata":"https://www.wikidata.org/wiki/Q188941","display_name":"Cell cycle","level":3,"score":0.22792735695838928},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.21867573261260986},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.21838125586509705},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.1809748113155365},{"id":"https://openalex.org/C2778019345","wikidata":"https://www.wikidata.org/wiki/Q1148337","display_name":"Hepatocellular carcinoma","level":2,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood.v118.21.3492.3492","doi":"https://doi.org/10.1182/blood.v118.21.3492.3492","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood.v118.21.3492.3492","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"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/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9537000060081482,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W1994026326","https://openalex.org/W3015749894","https://openalex.org/W3193559035","https://openalex.org/W2011853681","https://openalex.org/W4231049771","https://openalex.org/W2064901496","https://openalex.org/W2586067733","https://openalex.org/W2092880883","https://openalex.org/W2136680138","https://openalex.org/W2749281617"],"abstract_inverted_index":{"Abstract":[0,1],"3492":[2],"Mutations":[3],"of":[4,17,26,35,53,61,68,90,96,101,110,116,143,157,229,232,243,263,276,292,306,325,333,341,367,398,421,432,440,446,452,460,466,472,478,486,492,498,504,510,516,522,528],"the":[5,18,27,50,73,99,105,117,132,155,189,197,293,313,320,345,401,419,433],"FLT3":[6,28,62,97,106,111,134,190,217,277,315,368,399,434],"gene,":[7,107],"arising":[8],"from":[9,376],"internal":[10],"tandem":[11],"duplications":[12],"(\u2212ITD)":[13],"or":[14],"point":[15,166],"mutations":[16,39,55,103,431],"tyrosine":[19,30],"kinase":[20,31,63,250,404],"domain":[21],"(\u2212TKD),":[22],"cause":[23],"constitutive":[24],"activation":[25],"receptor":[29],"resulting":[32],"in":[33,44,104,138,321],"stimulation":[34],"leukemic":[36],"proliferation.":[37],"FLT3-ITD":[38,145,161,295],"confer":[40],"a":[41,66,163,204,273,410],"poor":[42],"prognosis":[43],"acute":[45],"myeloid":[46],"leukemia":[47],"(AML),":[48],"whilst":[49],"prognostic":[51],"impact":[52],"FLT3-TKD":[54,164],"remains":[56],"unclear.":[57],"Small":[58],"molecule":[59,94],"inhibition":[60,95,366,397],"has":[64,253,382],"been":[65,81],"focus":[67],"AML":[69,147,182,297,416],"drug":[70],"development":[71,100],"for":[72,216,414],"past":[74],"decade,":[75],"but":[76,195],"sustained":[77],"clinical":[78,390],"benefits":[79],"have":[80,122],"limited":[82],"by":[83,330,406,417,429],"pharmacokinetic":[84],"failures":[85],"and":[86,114,154,162,193,218,260,266,284,301,308,318,344,369,378,387,400,425],"resistance.":[87],"Important":[88],"mechanisms":[89],"resistance":[91,130,153,427],"to":[92,131,188,353],"small":[93],"include":[98],"secondary":[102,430],"elevated":[108],"levels":[109,128,332,424],"ligand":[112],"(FL)":[113],"over-expression":[115],"anti-apoptotic":[118],"protein,":[119],"Survivin.":[120,175],"We":[121],"previously":[123],"reported":[124],"that":[125,179],"high":[126,331,422],"FL":[127,423],"induce":[129],"selective":[133,215,314],"inhibitor":[135,200],"MLN518":[136,151,317],"(tandutinib)":[137],"vitro.":[139],"Furthermore,":[140,270],"prolonged":[141],"treatment":[142,412],"human":[144,294,385],"positive":[146,296],"cells":[148,158,183],"(MOLM-13)":[149],"with":[150,160,221,303,360,364],"caused":[152,428],"selection":[156],"doubly-mutated":[159,181,346],"(D835Y)":[165],"mutation.":[167],"These":[168],"resistant":[169,187],"cells,":[170],"termed":[171],"MOLM-13-RES,":[172],"also":[173,185,351],"over-express":[174],"Here":[176],"we":[177],"demonstrate":[178],"such":[180],"are":[184,350,392],"relatively":[186],"inhibitors":[191,316],"Sorafenib":[192],"AC220":[194],"not":[196,328],"dual":[198,365,396],"FLT3-Aurora":[199],"CCT241736.":[201],"CCT241736":[202,252,271,289,326,354,381,407],"is":[203,327],"novel,":[205],"orally":[206],"bioavailable,":[207],"imidazo[4,5-b]pyridine":[208],"derivative":[209],"discovered":[210],"at":[211,240,355],"our":[212],"Institute,":[213],"highly":[214],"Aurora":[219,258,261,370,405],"kinases":[220,235],"an":[222],"S(10)":[223],"selectivity":[224],"score":[225],"using":[226],"KINOMEscan\u2122":[227],"technology":[228],"0.057":[230],"(fraction":[231],"386":[233],"non-mutant":[234],"inhibited":[236],">90%":[237],"when":[238],"screened":[239],"1":[241],"uM":[242,268,310],"CCT241736;":[244],"San":[245],"Diego,":[246],"CA).":[247],"In":[248,286,335,394],"biochemical":[249],"studies,":[251],"IC50":[254],"values":[255,305],"against":[256],"FLT3,":[257],"A":[259],"B":[262],"0.035,":[264],"0.015":[265],"0.1":[267,307],"respectively.":[269,311],"inhibits":[272,290],"wide":[274],"range":[275],"mutants,":[278],"including":[279],"FLT3-ITD,":[280],"-D835Y,":[281],"-D835H,":[282],"-K663Q":[283],"\u2013N841I.":[285],"cellular":[287,323],"assays,":[288],"viability":[291],"cell":[298,347],"lines":[299],"MOLM-13":[300],"MV-4-11":[302],"EC50":[304],"0.27":[309],"Unlike":[312],"AC220,":[319],"vitro":[322],"efficacy":[324],"affected":[329],"FL.":[334],"vivo,":[336],"mouse":[337,377],"tumor":[338],"xenograft":[339],"models":[340],"MOLM-13,":[342],"MV-4-11,":[343],"line":[348],"MOLM-13-RES":[349],"sensitive":[352],"well":[356],"tolerated":[357],"oral":[358],"doses,":[359],"biomarker":[361],"modulation":[362],"consistent":[363],"kinases.":[371],"Based":[372],"on":[373],"allometric":[374],"scaling":[375],"rat":[379],"data,":[380],"favorable":[383],"predicted":[384],"pharmacokinetics":[386],"phase":[388],"I":[389],"trials":[391],"planned.":[393],"summary,":[395],"critical":[402],"mitotic":[403],"may":[408],"represent":[409],"novel":[411],"strategy":[413],"FLT3-mutated":[415],"overcoming":[418],"effects":[420],"limiting":[426],"gene.":[435],"Disclosures:":[436],"Moore:":[437],"The":[438],"Institute":[439,445,451,459,465,471,477,485,491,497,503,509,515,521,527],"Cancer":[441,447,453,461,467,473,479,487,493,499,505,511,517,523,529],"Research:":[442,448,454,462,468,474,480,488,494,500,506,512,518,524,530],"Employment.":[443,449,455,463,469,475,481,489,495,501,507,513,519,525,531],"Faisal:The":[444],"Bavetsias:The":[450],"Gonzalez":[456],"de":[457,482],"Castro:The":[458],"Sun:The":[464],"Atrash:The":[470],"Valenti:The":[476],"Haven":[483],"Brandon:The":[484],"Avery:The":[490],"Pearson:The":[496],"Workman:The":[502],"Blagg:The":[508],"Raynaud:The":[514],"Eccles:The":[520],"Linardopoulos:The":[526]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2015,"cited_by_count":1},{"year":2012,"cited_by_count":1}],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2019-10-18T00:00:00"}
