{"id":"https://openalex.org/W4240417600","doi":"https://doi.org/10.1158/1538-7445.sabcs18-359","title":"Abstract 359: Dual BET/kinase inhibitors as a novel strategy for the treatment of multiple myeloma","display_name":"Abstract 359: Dual BET/kinase inhibitors as a novel strategy for the treatment of multiple myeloma","publication_year":2019,"publication_date":"2019-07-01","ids":{"openalex":"https://openalex.org/W4240417600","doi":"https://doi.org/10.1158/1538-7445.sabcs18-359"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.sabcs18-359","doi":"https://doi.org/10.1158/1538-7445.sabcs18-359","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.sabcs18-359","pdf_url":null,"source":{"id":"https://openalex.org/S4306510252","display_name":"Experimental and Molecular Therapeutics","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Experimental and Molecular Therapeutics","raw_type":"proceedings-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/A5017977483","display_name":"Marilena Tauro","orcid":"https://orcid.org/0000-0003-2361-7364","observed_orcids":["https://orcid.org/0000-0003-2361-7364"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Marilena Tauro","raw_affiliation_strings":["Moffitt Cancer Center Research Institute, Tampa, FL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Moffitt Cancer Center Research Institute, Tampa, FL","institution_ids":["https://openalex.org/I3019308854"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5008138011","display_name":"Muhammad Ayaz","orcid":"https://orcid.org/0000-0002-4299-2445","observed_orcids":["https://orcid.org/0000-0002-4299-2445","https://orcid.org/0009-0002-2021-3735"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Muhammad Ayaz","raw_affiliation_strings":["Moffitt Cancer Center Research Institute, Tampa, FL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Moffitt Cancer Center Research Institute, Tampa, FL","institution_ids":["https://openalex.org/I3019308854"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5057921101","display_name":"Harshani R. Lawrence","orcid":"https://orcid.org/0000-0002-9263-7775","observed_orcids":["https://orcid.org/0000-0002-9263-7775"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Harshani R. Lawrence","raw_affiliation_strings":["Moffitt Cancer Center Research Institute, Tampa, FL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Moffitt Cancer Center Research Institute, Tampa, FL","institution_ids":["https://openalex.org/I3019308854"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5027503793","display_name":"Nicholas J. Lawrence","orcid":"https://orcid.org/0000-0003-1129-2558","observed_orcids":["https://orcid.org/0000-0003-1129-2558"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Nicholas J. Lawrence","raw_affiliation_strings":["Moffitt Cancer Center Research Institute, Tampa, FL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Moffitt Cancer Center Research Institute, Tampa, FL","institution_ids":["https://openalex.org/I3019308854"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5053572690","display_name":"Kenneth H. Shain","orcid":"https://orcid.org/0000-0003-4178-8888","observed_orcids":["https://orcid.org/0000-0003-4178-8888"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kenneth H. Shain","raw_affiliation_strings":["Moffitt Cancer Center Research Institute, Tampa, FL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Moffitt Cancer Center Research Institute, Tampa, FL","institution_ids":["https://openalex.org/I3019308854"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5024223427","display_name":"E. Sch\u00f6nbrunn","orcid":"https://orcid.org/0000-0002-3589-3510","observed_orcids":["https://orcid.org/0000-0002-3589-3510"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ernst Schonbrunn","raw_affiliation_strings":["Moffitt Cancer Center Research Institute, Tampa, FL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Moffitt Cancer Center Research Institute, Tampa, FL","institution_ids":["https://openalex.org/I3019308854"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5005942374","display_name":"Conor C. Lynch","orcid":"https://orcid.org/0000-0002-4506-6244","observed_orcids":["https://orcid.org/0000-0002-4506-6244"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Conor C. Lynch","raw_affiliation_strings":["Moffitt Cancer Center Research Institute, Tampa, FL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Moffitt Cancer Center Research Institute, Tampa, FL","institution_ids":["https://openalex.org/I3019308854"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I3019308854"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":"359","last_page":"359"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12534","display_name":"Protein Degradation and Inhibitors","score":0.9702000021934509,"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"}},"topics":[{"id":"https://openalex.org/T12534","display_name":"Protein Degradation and Inhibitors","score":0.9702000021934509,"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/T10649","display_name":"Multiple Myeloma Research and Treatments","score":0.028699999675154686,"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/T12820","display_name":"Chromatin Remodeling and Cancer","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"}}],"keywords":[{"id":"https://openalex.org/keywords/multiple-myeloma","display_name":"multiple myeloma","score":0.9929999709129333},{"id":"https://openalex.org/keywords/brd4-inhibition","display_name":"BRD4 inhibition","score":0.8320000171661377},{"id":"https://openalex.org/keywords/c-myc","display_name":"c-Myc","score":0.7480000257492065},{"id":"https://openalex.org/keywords/jq1","display_name":"JQ1","score":0.8399999737739563},{"id":"https://openalex.org/keywords/acquired-drug-resistance","display_name":"acquired drug resistance","score":0.7870000004768372},{"id":"https://openalex.org/keywords/jak2","display_name":"JAK2","score":0.6660000085830688},{"id":"https://openalex.org/keywords/flt3","display_name":"FLT3","score":0.8960000276565552},{"id":"https://openalex.org/keywords/ret","display_name":"RET","score":0.9919999837875366},{"id":"https://openalex.org/keywords/fgfr1","display_name":"FGFR1","score":0.9850000143051147},{"id":"https://openalex.org/keywords/ulk3","display_name":"ULK3","score":0.8840000033378601},{"id":"https://openalex.org/keywords/autophagy-inhibition","display_name":"autophagy inhibition","score":0.9100000262260437},{"id":"https://openalex.org/keywords/autophagy-related-proteins","display_name":"autophagy-related proteins","score":0.777999997138977},{"id":"https://openalex.org/keywords/cellular-senescence","display_name":"cellular senescence","score":0.7099999785423279},{"id":"https://openalex.org/keywords/overall-survival","display_name":"overall survival","score":0.5009999871253967},{"id":"https://openalex.org/keywords/epigenetic-regulation","display_name":"epigenetic regulation","score":0.5120000243186951}],"concepts":[{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5150587558746338},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.46941766142845154},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.465340256690979},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.4467525780200958},{"id":"https://openalex.org/C2776364478","wikidata":"https://www.wikidata.org/wiki/Q467635","display_name":"Multiple myeloma","level":2,"score":0.439873069524765},{"id":"https://openalex.org/C74401373","wikidata":"https://www.wikidata.org/wiki/Q1829843","display_name":"Bromodomain","level":4,"score":0.4320200979709625},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3876815140247345},{"id":"https://openalex.org/C41091548","wikidata":"https://www.wikidata.org/wiki/Q26939","display_name":"Epigenetics","level":3,"score":0.3698461651802063},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.35249102115631104},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.2971928119659424},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.25203853845596313},{"id":"https://openalex.org/C150903083","wikidata":"https://www.wikidata.org/wiki/Q7108","display_name":"Biotechnology","level":1,"score":0.09165585041046143},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.06856617331504822},{"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.sabcs18-359","doi":"https://doi.org/10.1158/1538-7445.sabcs18-359","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.sabcs18-359","pdf_url":null,"source":{"id":"https://openalex.org/S4306510252","display_name":"Experimental and Molecular Therapeutics","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Experimental and Molecular Therapeutics","raw_type":"proceedings-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":[],"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/W2750537303","https://openalex.org/W2599917498","https://openalex.org/W2341810480","https://openalex.org/W2588683607","https://openalex.org/W2561742237","https://openalex.org/W2549779868","https://openalex.org/W4362595174","https://openalex.org/W2585129131","https://openalex.org/W2588726445","https://openalex.org/W2890306273"],"abstract_inverted_index":{"The":[0],"bromodomain":[1],"and":[2,30,83,99,114,134,182,227,242,258,318,326,380],"extra-terminal":[3],"(BET)":[4],"family":[5],"of":[6,12,75,86,126,223,268,311,365,384,410,443,449],"proteins":[7,290],"are":[8,130],"important":[9],"epigenetic":[10],"regulators":[11],"critical":[13],"oncogenes,":[14],"including":[15,93],"c-Myc.":[16],"JQ1":[17,58,157,181],"is":[18,41,124,237,279,338,349],"the":[19,109,183,206,220,266,272,340,363,366,382,385,441,450],"most":[20],"potent":[21],"BRD4":[22,55,82,113],"inhibitor,":[23],"currently":[24],"used":[25],"in":[26,32,37,91,103,132,200,205,239,271,362,387],"several":[27,250],"clinical":[28,39],"trials":[29],"effective":[31],"preventing":[33],"multiple":[34,376,390,407,444],"myeloma":[35,201,377,391,408,445],"progression":[36,364],"vivo.Currently,":[38],"data":[40,275],"showing":[42,112],"that":[43,50,129,170,277,299],"patients":[44],"often":[45],"develop":[46],"acquired":[47],"resistance,":[48],"indicating":[49],"single":[51,411],"agent":[52],"therapies":[53],"targeting":[54,225],"such":[56],"as":[57,108,210,219,284,401,436],"may":[59],"not":[60,332],"provide":[61],"durable":[62],"therapeutic":[63],"responses.":[64],"To":[65],"overcome":[66],"this":[67,360],"limitation,":[68],"we":[69,264],"have":[70],"developed":[71],"a":[72,84,197,245,402,437],"new":[73],"class":[74],"dual":[76,398],"inhibitors,":[77],"capable":[78,125],"to":[79,119,156,176,180,261,286,293,358,405],"simultaneously":[80],"target":[81,361],"panel":[85],"tyrosine":[87],"kinases":[88,128],"highly":[89],"expressed":[90],"cancer":[92,133,251,354],"JAK2,":[94],"FLT3,":[95],"RET,":[96],"FGFR1,":[97],"ULK1":[98],"ULK3.":[100],"A":[101],"preliminary":[102],"vitro":[104,141],"screening":[105],"identified":[106,217],"SG3-014":[107,149,171,207,224,269,278,303,344],"lead":[110],"compound,":[111],"c-Myc":[115],"inhibition":[116,270,400],"activity":[117,226,346],"similar":[118],"JQ1,":[120,287],"but":[121],"additionally,":[122],"it":[123],"inhibiting":[127],"over-activated":[131],"responsible":[135,350],"for":[136,351,440,453],"cytokine-mediated":[137],"drug":[138],"resistance":[139],"pathways.In":[140],"assays":[142],"on":[143,347],"MM":[144,232],"cell":[145,252,355],"lines":[146,253],"reveals":[147],"higher":[148],"sensitivity":[150],"(5TGM1,":[151,158],"0.85\u03bcM;":[152],"U266,":[153,160],"0.99\u03bcM)":[154],"compared":[155,179],"4.7\u03bcM;":[159],"16\u03bcM).":[161],"In":[162],"vivo":[163,375],"studies":[164],"using":[165],"1x106":[166],"5TGM1-Luc":[167],"cells":[168,392],"demonstrate":[169],"treatment":[172,442],"(25mg/Kg)":[173],"significantly":[174],"contributes":[175],"overall":[177],"survival":[178,189],"vehicle":[184],"control":[185],"cohort":[186],"(n=10/group)":[187],"(median":[188],"CTRL=40.5;":[190],"SG3-014=50.5;":[191],"JQ1=46":[192],"days).":[193],"Post-study":[194],"analyses":[195],"demonstrated":[196],"significant":[198],"reduction":[199],"induced":[202],"bone":[203],"disease":[204,233],"treated":[208],"mice":[209],"measured":[211],"by":[212,248,324,342],"X-ray/":[213],"\u03bcCT/":[214],"histomorphometry.Clinical":[215],"datasets":[216],"ULK3":[218,236,348],"candidate":[221],"kinase":[222],"correlated":[228],"its":[229],"expression":[230],"with":[231,308,334],"stages.":[234],"Since":[235],"involved":[238],"cellular":[240],"senescence":[241],"autophagy":[243,273,281,307,352],"regulation,":[244],"key":[246],"mechanism":[247,341],"which":[249,343],"protect":[254],"themselves":[255],"against":[256],"apoptosis":[257],"become":[259],"resistant":[260],"standard":[262],"treatments,":[263],"explored":[265],"role":[267],"pathway.Preliminary":[274],"confirm":[276],"an":[280],"inhibitor":[282,386],"and,":[283],"opposed":[285],"downregulates":[288],"ATG":[289],"level,":[291],"leading":[292],"dysfunctional":[294],"autophagosome":[295],"formation.":[296],"We":[297],"noted":[298,333],"within":[300],"6":[301],"h,":[302],"completely":[304],"shut":[305],"down":[306],"decrease":[309],"levels":[310],"ULK1,":[312],"beclin-1,":[313],"ATG16L-1,":[314],"ATG12,":[315],"ATG3,":[316],"p62":[317],"increased":[319],"LC3I/II":[320],"ratios":[321],"(additionally":[322],"confirmed":[323],"microscopy":[325],"flow":[327],"cytometry).":[328],"These":[329],"effects":[330],"were":[331],"JQ1.":[335],"Further":[336],"investigation":[337],"clarifying":[339],"inhibitory":[345],"mediated":[353],"death.In":[356],"order":[357],"validate":[359],"human":[367],"disease,":[368],"our":[369],"future":[370],"directions":[371],"will":[372],"analyze":[373],"ex":[374],"patient":[378,395],"samples":[379],"examine":[381],"efficacy":[383],"CD138":[388],"isolated":[389],"derived":[393],"from":[394],"biopsies.We":[396],"propose":[397],"BRD4/autophagy":[399],"resilient":[403],"strategy":[404,439],"prevent":[406],"by-pass":[409],"targeted":[412],"therapies.Citation":[413],"Format:":[414],"Marilena":[415],"Tauro,":[416],"Muhammad":[417],"Ayaz,":[418],"Harshani":[419],"R.":[420],"Lawrence,":[421,424],"Nicholas":[422],"J.":[423],"Kenneth":[425],"H.":[426],"Shain,":[427],"Ernst":[428],"Schonbrunn,":[429],"Conor":[430],"C.":[431],"Lynch.":[432],"Dual":[433],"BET/kinase":[434],"inhibitors":[435],"novel":[438],"[abstract].":[446],"In:":[447],"Proceedings":[448],"American":[451],"Association":[452],"Cancer":[454,468],"Research":[455],"Annual":[456],"Meeting":[457],"2019;":[458],"2019":[459],"Mar":[460],"29-Apr":[461],"3;":[462],"Atlanta,":[463],"GA.":[464],"Philadelphia":[465],"(PA):":[466],"AACR;":[467],"Res":[469],"2019;79(13":[470],"Suppl):Abstract":[471],"nr":[472],"359.":[473]},"counts_by_year":[],"updated_date":"2026-10-01T08:54:57.152042","created_date":"2022-05-12T00:00:00"}