{"id":"https://openalex.org/W2485580653","doi":"https://doi.org/10.1158/1538-7445.am2015-1612","title":"Abstract 1612: Identification of mithramycin analogs with improved targeting of the EWS/FLI1 transcription factor","display_name":"Abstract 1612: Identification of mithramycin analogs with improved targeting of the EWS/FLI1 transcription factor","publication_year":2015,"publication_date":"2015-08-01","ids":{"openalex":"https://openalex.org/W2485580653","doi":"https://doi.org/10.1158/1538-7445.am2015-1612","mag":"2485580653"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2015-1612","doi":"https://doi.org/10.1158/1538-7445.am2015-1612","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2015-1612","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":"conference-abstract","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/A5030426478","display_name":"Christy L. Osgood","orcid":"https://orcid.org/0000-0001-7450-9342","observed_orcids":["https://orcid.org/0000-0001-7450-9342"]},"institutions":[{"id":"https://openalex.org/I200719446","display_name":"Vanderbilt University","ror":"https://ror.org/02vm5rt34","country_code":"US","type":"education","lineage":["https://openalex.org/I200719446"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Christy Osgood","raw_affiliation_strings":["1Vanderbilt University, Nashville, TN;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Vanderbilt University, Nashville, TN;","institution_ids":["https://openalex.org/I200719446"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5065627176","display_name":"Nichole Maloney","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I200719446","display_name":"Vanderbilt University","ror":"https://ror.org/02vm5rt34","country_code":"US","type":"education","lineage":["https://openalex.org/I200719446"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Nichole Maloney","raw_affiliation_strings":["1Vanderbilt University, Nashville, TN;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Vanderbilt University, Nashville, TN;","institution_ids":["https://openalex.org/I200719446"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5008226118","display_name":"Christopher G. Kidd","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I200719446","display_name":"Vanderbilt University","ror":"https://ror.org/02vm5rt34","country_code":"US","type":"education","lineage":["https://openalex.org/I200719446"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Christopher G. Kidd","raw_affiliation_strings":["1Vanderbilt University, Nashville, TN;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Vanderbilt University, Nashville, TN;","institution_ids":["https://openalex.org/I200719446"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081182847","display_name":"Meti Gebregiorgis","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210140884","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Meti Gebregiorgis","raw_affiliation_strings":["2National Cancer Institute, Bethesda, MD;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2National Cancer Institute, Bethesda, MD;","institution_ids":["https://openalex.org/I4210140884"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5109168840","display_name":"Luz Elena N\u00fa\u00f1ez","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210166067","display_name":"EntreChem (Spain)","ror":"https://ror.org/05vj0gw61","country_code":"ES","type":"company","lineage":["https://openalex.org/I4210166067"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Luz E. Nunez","raw_affiliation_strings":["3EntreChem, Ls, Oviedo, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"3EntreChem, Ls, Oviedo, Spain","institution_ids":["https://openalex.org/I4210166067"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5059473358","display_name":"Javier Gonz\u00e1lez\u2010Sab\u00edn","orcid":"https://orcid.org/0000-0003-3764-4750","observed_orcids":["https://orcid.org/0000-0003-3764-4750"]},"institutions":[{"id":"https://openalex.org/I4210166067","display_name":"EntreChem (Spain)","ror":"https://ror.org/05vj0gw61","country_code":"ES","type":"company","lineage":["https://openalex.org/I4210166067"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Javier Gonzalez-Sabin","raw_affiliation_strings":["3EntreChem, Ls, Oviedo, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"3EntreChem, Ls, Oviedo, Spain","institution_ids":["https://openalex.org/I4210166067"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066585382","display_name":"Lee J. Helman","orcid":"https://orcid.org/0000-0001-9553-4475","observed_orcids":["https://orcid.org/0000-0001-9553-4475"]},"institutions":[{"id":"https://openalex.org/I4210140884","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210140884"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Lee J. Helman","raw_affiliation_strings":["2National Cancer Institute, Bethesda, MD;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2National Cancer Institute, Bethesda, MD;","institution_ids":["https://openalex.org/I4210140884"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5068607171","display_name":"Francisco Mor\u00eds","orcid":"https://orcid.org/0000-0002-4702-6879","observed_orcids":["https://orcid.org/0000-0002-4702-6879"]},"institutions":[{"id":"https://openalex.org/I4210166067","display_name":"EntreChem (Spain)","ror":"https://ror.org/05vj0gw61","country_code":"ES","type":"company","lineage":["https://openalex.org/I4210166067"]}],"countries":["ES"],"is_corresponding":false,"raw_author_name":"Francisco Moris","raw_affiliation_strings":["3EntreChem, Ls, Oviedo, Spain"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"3EntreChem, Ls, Oviedo, Spain","institution_ids":["https://openalex.org/I4210166067"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5028721392","display_name":"Patrick Joseph Grohar","orcid":"https://orcid.org/0000-0002-1071-4563","observed_orcids":["https://orcid.org/0000-0002-1071-4563"]},"institutions":[{"id":"https://openalex.org/I200719446","display_name":"Vanderbilt University","ror":"https://ror.org/02vm5rt34","country_code":"US","type":"education","lineage":["https://openalex.org/I200719446"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Patrick J. Grohar","raw_affiliation_strings":["1Vanderbilt University, Nashville, TN;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Vanderbilt University, Nashville, TN;","institution_ids":["https://openalex.org/I200719446"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":2,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"75","issue":"15_Supplement","first_page":"1612","last_page":"1612"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10253","display_name":"Sarcoma Diagnosis and Treatment","score":0.9922000169754028,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"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/T10253","display_name":"Sarcoma Diagnosis and Treatment","score":0.9922000169754028,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"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":0.0005000000237487257,"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/T12477","display_name":"Toxin Mechanisms and Immunotoxins","score":0.00039999998989515007,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/ews-fli1","display_name":"EWS-FLI1","score":0.8790000081062317},{"id":"https://openalex.org/keywords/ewing-sarcoma","display_name":"Ewing sarcoma","score":0.9980000257492065},{"id":"https://openalex.org/keywords/small-molecule-inhibitors","display_name":"small molecule inhibitors","score":0.6039999723434448},{"id":"https://openalex.org/keywords/hepatotoxicity","display_name":"hepatotoxicity","score":0.906000018119812},{"id":"https://openalex.org/keywords/drug-toxicity","display_name":"drug toxicity","score":0.47099998593330383},{"id":"https://openalex.org/keywords/chromatin-binding","display_name":"chromatin binding","score":0.8029999732971191},{"id":"https://openalex.org/keywords/transcription-factor-inhibition","display_name":"transcription factor inhibition","score":0.5809999704360962},{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"pharmacokinetics","score":0.5989999771118164},{"id":"https://openalex.org/keywords/high-throughput-screening","display_name":"high-throughput screening","score":0.5619999766349792},{"id":"https://openalex.org/keywords/drug-repurposing","display_name":"drug repurposing","score":0.5929999947547913}],"concepts":[{"id":"https://openalex.org/C2777937962","wikidata":"https://www.wikidata.org/wiki/Q17928801","display_name":"FLI1","level":4,"score":0.7096799612045288},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.6422486305236816},{"id":"https://openalex.org/C86339819","wikidata":"https://www.wikidata.org/wiki/Q407384","display_name":"Transcription factor","level":3,"score":0.5073117613792419},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.49695947766304016},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.4816288352012634},{"id":"https://openalex.org/C2778256501","wikidata":"https://www.wikidata.org/wiki/Q223911","display_name":"Sarcoma","level":2,"score":0.4799233078956604},{"id":"https://openalex.org/C2776415932","wikidata":"https://www.wikidata.org/wiki/Q48743","display_name":"Western blot","level":3,"score":0.47205907106399536},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.44600075483322144},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.42934364080429077},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.33599352836608887},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.28812018036842346},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.1185724139213562},{"id":"https://openalex.org/C142724271","wikidata":"https://www.wikidata.org/wiki/Q7208","display_name":"Pathology","level":1,"score":0.11500197649002075},{"id":"https://openalex.org/C150903083","wikidata":"https://www.wikidata.org/wiki/Q7108","display_name":"Biotechnology","level":1,"score":0.0},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2015-1612","doi":"https://doi.org/10.1158/1538-7445.am2015-1612","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2015-1612","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"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9476000070571899,"display_name":"Good health and well-being"}],"sustainable_development_goals_aurora":[{"id":"https://metadata.un.org/sdg/3","score":0.5400000214576721,"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/W2301394599","https://openalex.org/W2333069942","https://openalex.org/W2567634610","https://openalex.org/W4389239989","https://openalex.org/W2068155537","https://openalex.org/W3046964403","https://openalex.org/W4409630868","https://openalex.org/W2981093800","https://openalex.org/W3137159641","https://openalex.org/W2796761685"],"abstract_inverted_index":{"Abstract":[0],"Background:":[1],"Ewing":[2,243,344],"sarcoma":[3,10,244,345],"is":[4,98,268,290,412],"a":[5,7,12,47,67,132,136,349],"bone":[6],"soft":[8],"tissue":[9,255],"with":[11,348,442],"poor":[13],"overall":[14],"survival.":[15,31],"This":[16],"tumor":[17,237],"absolutely":[18],"depends":[19],"on":[20,36],"the":[21,25,64,77,93,172,187,197,215,230,273,297,305,367,385,406,446,454,459],"continued":[22],"expression":[23],"of":[24,57,73,95,138,171,191,196,209,214,232,242,248,252,264,280,304,343,357,409,439,445,453,458],"EWS-FLI1":[26,58,148,156,176,210,249,265,306,314,327,374,390],"transcription":[27,448],"factor":[28],"for":[29,462],"cell":[30],"We":[32,43,364],"are":[33,332,378],"therefore":[34],"focused":[35],"developing":[37],"small":[38],"molecules":[39],"that":[40,51,87,206,331,393,405],"inhibit":[41],"EWS-FLI1.":[42],"have":[44,365],"previously":[45],"completed":[46],"high":[48],"throughput":[49],"screen":[50],"identified":[52,115,366],"mithramycin":[53,106,142,368,440],"as":[54,373],"an":[55,147],"inhibitor":[56],"and":[59,121,126,163,189,220,245,300,355,371,381,388],"translated":[60],"this":[61,74,96],"compound":[62,75,299,387],"to":[63,99,130,153,174,178,211,235,312,316,322,334,397],"clinic":[65,78],"in":[66,76,124,167,186,201,217,222,224,239,282,284,320,352,360],"phase":[68],"I-II":[69],"trial.":[70],"The":[71,109,169,193],"success":[72],"has":[79,88],"been":[80],"challenged":[81],"by":[82,116,182,203],"drug":[83,173,216,281],"associated":[84],"liver":[85,399],"toxicity":[86,119],"necessitated":[89],"dose":[90],"reductions.":[91],"Therefore":[92],"goal":[94],"study":[97],"identify":[100,131,154],"less":[101,110,270,379],"toxic":[102,111,212,271,380],"and-or":[103],"more":[104,133,139,294,382],"potent":[105,134,295,383],"analogs.":[107],"Methods:":[108],"analog,":[112],"EC8042,":[113],"was":[114,144,158,180,199],"evaluating":[117],"animal":[118,285],"data":[120],"serum":[122,278],"pharmacokinetics":[123],"mice":[125],"rats.":[127],"In":[128,287],"order":[129],"compound,":[135,275],"panel":[137],"than":[140,272,296,384],"20":[141],"analogs":[143,198,234,325,369,411,441],"screened":[145],"using":[146,160,250],"reporter":[149],"NR0B1":[150],"luciferase":[151],"construct":[152],"EC8105.":[155],"suppression":[157,208,247,263,303,342],"confirmed":[159,221,246],"quantitative":[161],"PCR":[162],"western":[164],"blot":[165],"analysis":[166],"vitro.":[168],"ability":[170,231],"block":[175,313],"binding":[177,315],"chromatin":[179,184],"evaluated":[181],"performing":[183],"immunoprecipitation":[185],"presence":[188],"absence":[190],"drug.":[192],"relative":[194],"hepatotoxicity":[195],"modeled":[200],"vitro":[202],"comparing":[204],"doses":[205,213],"achieve":[207],"HepG2":[218,335],"cells":[219],"vivo":[223,283],"xenograft":[225,240,346],"experiments.":[226,258],"Finally,":[227],"we":[228],"tested":[229],"both":[233,324,361],"suppress":[236,326,389],"growth":[238,347],"models":[241],"immunofluorescence":[251],"formalin":[253],"fixed":[254],"from":[256],"these":[257,402,410],"Results:":[259],"EC8042":[260,370],"shows":[261],"equivalent":[262],"activity":[266,328],"but":[267],"substantially":[269],"parent":[274,298,386],"allowing":[276],"higher":[277],"levels":[279],"models.":[286],"contrast,":[288],"EC8105":[289,372],"approximately":[291],"8":[292],"times":[293],"demonstrates":[301],"improved":[302,341,443],"gene":[307],"signature.":[308],"Both":[309],"compounds":[310,377],"work":[311],"chromatin.":[317],"More":[318],"importantly,":[319],"contrast":[321],"mithramycin,":[323],"at":[329,391],"concentrations":[330,392],"non-toxic":[333],"cells.":[336],"These":[337,376],"effects":[338],"translate":[339],"into":[340],"corresponding":[350],"increase":[351],"mouse":[353],"survival":[354],"regression":[356],"several":[358],"tumors":[359],"cohorts.":[362],"Conclusions:":[363],"inhibitors.":[375],"do":[394],"not":[395],"appear":[396],"cause":[398],"toxicity.":[400],"Together":[401],"results":[403],"suggest":[404],"clinical":[407],"development":[408],"warranted.":[413],"Citation":[414],"Format:":[415],"Christy":[416],"Osgood,":[417],"Nichole":[418],"Maloney,":[419],"Christopher":[420],"G.":[421],"Kidd,":[422],"Meti":[423],"Gebregiorgis,":[424],"Luz":[425],"E.":[426],"Nunez,":[427],"Javier":[428],"Gonzalez-Sabin,":[429],"Lee":[430],"J.":[431,436],"Helman,":[432],"Francisco":[433],"Moris,":[434],"Patrick":[435],"Grohar.":[437],"Identification":[438],"targeting":[444],"EWS/FLI1":[447],"factor.":[449],"[abstract].":[450],"In:":[451],"Proceedings":[452],"106th":[455],"Annual":[456],"Meeting":[457],"American":[460],"Association":[461],"Cancer":[463,473],"Research;":[464],"2015":[465],"Apr":[466],"18-22;":[467],"Philadelphia,":[468],"PA.":[469],"Philadelphia":[470],"(PA):":[471],"AACR;":[472],"Res":[474],"2015;75(15":[475],"Suppl):Abstract":[476],"nr":[477],"1612.":[478],"doi:10.1158/1538-7445.AM2015-1612":[479]},"counts_by_year":[{"year":2016,"cited_by_count":2}],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2016-08-23T00:00:00"}