{"id":"https://openalex.org/W4380029965","doi":"https://doi.org/10.1158/1538-7445.am2023-5018","title":"Abstract 5018: PROTAC degraders of CDK8/CDK19 Mediator kinases potently suppress multiple myeloma proliferation","display_name":"Abstract 5018: PROTAC degraders of CDK8/CDK19 Mediator kinases potently suppress multiple myeloma proliferation","publication_year":2023,"publication_date":"2023-04-04","ids":{"openalex":"https://openalex.org/W4380029965","doi":"https://doi.org/10.1158/1538-7445.am2023-5018"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2023-5018","doi":"https://doi.org/10.1158/1538-7445.am2023-5018","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2023-5018","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":null,"display_name":"Li Zhang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I155781252","display_name":"University of South Carolina","ror":"https://ror.org/02b6qw903","country_code":"US","type":"education","lineage":["https://openalex.org/I155781252"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Li Zhang","raw_affiliation_strings":["1University of South Carolina, Columbia, SC;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of South Carolina, Columbia, SC;","institution_ids":["https://openalex.org/I155781252"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100337073","display_name":"Jing Li","orcid":"https://orcid.org/0000-0003-2065-9040","observed_orcids":["https://orcid.org/0000-0003-2065-9040"]},"institutions":[{"id":"https://openalex.org/I155781252","display_name":"University of South Carolina","ror":"https://ror.org/02b6qw903","country_code":"US","type":"education","lineage":["https://openalex.org/I155781252"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jing Li","raw_affiliation_strings":["1University of South Carolina, Columbia, SC;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of South Carolina, Columbia, SC;","institution_ids":["https://openalex.org/I155781252"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5073198850","display_name":"Charles E. Dowling","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I155781252","display_name":"University of South Carolina","ror":"https://ror.org/02b6qw903","country_code":"US","type":"education","lineage":["https://openalex.org/I155781252"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Charles E. Dowling","raw_affiliation_strings":["1University of South Carolina, Columbia, SC;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of South Carolina, Columbia, SC;","institution_ids":["https://openalex.org/I155781252"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5049867556","display_name":"Eugenia V. Broude","orcid":"https://orcid.org/0000-0002-9180-7111","observed_orcids":["https://orcid.org/0000-0002-9180-7111"]},"institutions":[{"id":"https://openalex.org/I155781252","display_name":"University of South Carolina","ror":"https://ror.org/02b6qw903","country_code":"US","type":"education","lineage":["https://openalex.org/I155781252"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Eugenia V. Broude","raw_affiliation_strings":["1University of South Carolina, Columbia, SC;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of South Carolina, Columbia, SC;","institution_ids":["https://openalex.org/I155781252"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5006208805","display_name":"Igor B. Roninson","orcid":"https://orcid.org/0000-0002-9211-1327","observed_orcids":["https://orcid.org/0000-0002-9211-1327"]},"institutions":[{"id":"https://openalex.org/I155781252","display_name":"University of South Carolina","ror":"https://ror.org/02b6qw903","country_code":"US","type":"education","lineage":["https://openalex.org/I155781252"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Igor B. Roninson","raw_affiliation_strings":["1University of South Carolina, Columbia, SC;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of South Carolina, Columbia, SC;","institution_ids":["https://openalex.org/I155781252"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110026436","display_name":"Campbell McInnes","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I155781252","display_name":"University of South Carolina","ror":"https://ror.org/02b6qw903","country_code":"US","type":"education","lineage":["https://openalex.org/I155781252"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Campbell McInnes","raw_affiliation_strings":["1University of South Carolina, Columbia, SC;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of South Carolina, Columbia, SC;","institution_ids":["https://openalex.org/I155781252"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5028090148","display_name":"Mengqian Chen","orcid":"https://orcid.org/0000-0003-1706-9509","observed_orcids":["https://orcid.org/0000-0003-1706-9509"]},"institutions":[{"id":"https://openalex.org/I4210157231","display_name":"Senex Biotechnology (United States)","ror":"https://ror.org/05w1q8228","country_code":"US","type":"company","lineage":["https://openalex.org/I4210157231"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mengqian Chen","raw_affiliation_strings":["2Senex Biotechnology, Columbia, SC"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Senex Biotechnology, Columbia, SC","institution_ids":["https://openalex.org/I4210157231"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"83","issue":"7_Supplement","first_page":"5018","last_page":"5018"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12534","display_name":"Protein Degradation and Inhibitors","score":0.9994999766349792,"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":0.9994999766349792,"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":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"}},{"id":"https://openalex.org/T10543","display_name":"Prostate Cancer Treatment and Research","score":0.0,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/protacs","display_name":"PROTACs","score":0.6700000166893005},{"id":"https://openalex.org/keywords/cdk8","display_name":"CDK8","score":0.843999981880188},{"id":"https://openalex.org/keywords/cdk19","display_name":"CDK19","score":1.0},{"id":"https://openalex.org/keywords/mediator-complex","display_name":"Mediator complex","score":0.7710000276565552},{"id":"https://openalex.org/keywords/cyclin-c","display_name":"cyclin C","score":0.7590000033378601},{"id":"https://openalex.org/keywords/multiple-myeloma","display_name":"multiple myeloma","score":0.972000002861023},{"id":"https://openalex.org/keywords/pomalidomide","display_name":"pomalidomide","score":0.7279999852180481},{"id":"https://openalex.org/keywords/cancer-dependency-map","display_name":"DepMap","score":0.39899998903274536},{"id":"https://openalex.org/keywords/kinase-inhibitors","display_name":"kinase inhibitors","score":0.41100001335144043},{"id":"https://openalex.org/keywords/drug-repurposing","display_name":"drug repurposing","score":0.5040000081062317},{"id":"https://openalex.org/keywords/transcriptional-regulation","display_name":"transcriptional regulation","score":0.4020000100135803},{"id":"https://openalex.org/keywords/antiproliferative-activity","display_name":"antiproliferative activity","score":0.6029999852180481}],"concepts":[{"id":"https://openalex.org/C116227048","wikidata":"https://www.wikidata.org/wiki/Q18021243","display_name":"Cyclin-dependent kinase 8","level":4,"score":0.7758206725120544},{"id":"https://openalex.org/C124320809","wikidata":"https://www.wikidata.org/wiki/Q46292","display_name":"Cyclin-dependent kinase","level":4,"score":0.628156840801239},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.6052994728088379},{"id":"https://openalex.org/C94734110","wikidata":"https://www.wikidata.org/wiki/Q18021240","display_name":"Cyclin-dependent kinase 7","level":5,"score":0.46930626034736633},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.43901699781417847},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.40793949365615845},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.37877434492111206},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.35070711374282837},{"id":"https://openalex.org/C97029542","wikidata":"https://www.wikidata.org/wiki/Q281417","display_name":"Protein kinase A","level":3,"score":0.2863169312477112},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.28042852878570557},{"id":"https://openalex.org/C82495950","wikidata":"https://www.wikidata.org/wiki/Q14911732","display_name":"Cyclin-dependent kinase 2","level":4,"score":0.2608432173728943},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.1949552297592163},{"id":"https://openalex.org/C29537977","wikidata":"https://www.wikidata.org/wiki/Q188941","display_name":"Cell cycle","level":3,"score":0.17078426480293274},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.13898524641990662},{"id":"https://openalex.org/C161879069","wikidata":"https://www.wikidata.org/wiki/Q904082","display_name":"Notch signaling pathway","level":3,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2023-5018","doi":"https://doi.org/10.1158/1538-7445.am2023-5018","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2023-5018","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":[{"display_name":"Good health and well-being","score":0.8048999905586243,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W7149031557","https://openalex.org/W7016151164","https://openalex.org/W2740828062","https://openalex.org/W2965701656","https://openalex.org/W3111821491","https://openalex.org/W7204999020","https://openalex.org/W4389242887","https://openalex.org/W2625751604","https://openalex.org/W2559977427","https://openalex.org/W2500944099"],"abstract_inverted_index":{"Abstract":[0],"CDK8":[1,13,129,303],"and":[2,24,53,78,87,130,220,232,309,371],"CDK19":[3,15,131],"are":[4],"kinase":[5,69,150,168,174,230,259],"components":[6,52],"of":[7,49,84,98,108,138,143,158,166,206,253,268,279,286,317,323,346,358],"the":[8,28,59,82,156,159,164,167,173,207,258,262,274,287,315,321,359],"CDK":[9,29],"module":[10,30],"that":[11,155,188],"comprises":[12],"or":[14,152,301],"together":[16],"with":[17,33,136,147],"their":[18,90],"binding":[19,118],"partner":[20],"cyclin":[21],"C":[22],"(CCNC)":[23],"two":[25,214,263],"other":[26],"proteins;":[27],"is":[31,62,194],"associated":[32],"transcriptional":[34],"Mediator":[35,38,50,348],"complex.":[36],"CDK8/19":[37,68,85,109,149,229,248],"kinases":[39,349],"potentiate":[40],"transcription":[41],"induced":[42,179],"by":[43],"different":[44,105,113,133,228],"signals,":[45],"regulate":[46],"protein":[47],"levels":[48],"complex":[51],"protect":[54],"CCNC":[55,180,203],"from":[56],"proteolytic":[57],"degradation;":[58],"latter":[60],"activity":[61,241],"exerted":[63],"in":[64,132,242,261,273],"a":[65,116,148,294,302],"kinase-independent":[66,91],"manner.":[67],"inhibitors":[70,107,231,235,260],"have":[71,94,212],"entered":[72],"clinical":[73],"trials":[74],"for":[75,225,292,320,362],"solid":[76],"tumors":[77],"leukemias.":[79],"To":[80],"extend":[81],"effects":[83,162,165,278],"inhibition":[86],"to":[88,115,172,227,238],"suppress":[89,351],"activities,":[92],"we":[93],"developed":[95],"three":[96,244],"series":[97],"PROteolysis":[99],"TArgeting":[100],"Chimeras":[101],"(PROTACs)":[102],"based":[103],"on":[104,202,298],"selective":[106],"kinases,":[110],"connected":[111],"via":[112],"linkers":[114],"moiety":[117],"cereblon":[119],"(CRBN)":[120],"E3":[121],"ligase.":[122],"The":[123,277],"most":[124,205],"potent":[125,256],"PROTACs":[126,177,249,281,319],"degraded":[127],"both":[128],"cell":[134,209,218],"types":[135],"DC50s":[137],"10-20":[139],"nM.":[140],"RNA-Seq":[141],"analysis":[142,186],"293":[144],"cells":[145],"treated":[146],"inhibitor":[151],"PROTAC":[153,296,305,344],"showed":[154,236],"bulk":[157],"PROTAC\u2019s":[160],"transcriptomic":[161],"matched":[163],"inhibitor.":[169],"In":[170],"contrast":[171],"inhibitors,":[175],"CDK8/19-degrading":[176,280],"also":[178],"degradation.":[181],"Cancer":[182,363,382],"Dependency":[183],"Map":[184],"(DepMap)":[185],"revealed":[187],"multiple":[189,352],"myelomas":[190],"(MM),":[191],"where":[192],"CRBN":[193],"an":[195,251],"established":[196],"therapeutic":[197],"target,":[198],"show":[199],"greater":[200],"dependency":[201],"than":[204,257,284],"tumor":[208],"lines.":[210],"We":[211],"tested":[213],"strongly":[215],"CCNC-dependent":[216,264],"MM":[217,223,245,265],"lines":[219,266],"one":[221],"CCNC-independent":[222,275],"line":[224],"sensitivity":[226],"PROTACs.":[233],"Kinase":[234],"low":[237],"moderate":[239],"anti-proliferative":[240],"all":[243],"lines,":[246],"whereas":[247],"were":[250,282],"order":[252],"magnitude":[254],"more":[255],"(IC50s":[267],"20-30":[269],"nM)":[270],"but":[271],"not":[272],"line.":[276],"stronger":[283],"those":[285],"CRBN-targeting":[288],"drug":[289],"pomalidomide":[290],"(approved":[291],"MM),":[293],"CRBN-binding":[295,310],"acting":[297],"androgen":[299],"receptor":[300],"degradation-inactive":[304],"analog":[306],"containing":[307],"CDK8/19-":[308],"moieties.":[311],"These":[312],"results":[313],"suggest":[314],"potential":[316],"CDK8/CDK19-degrading":[318],"treatment":[322],"MM.":[324],"Citation":[325],"Format:":[326],"Li":[327],"Zhang,":[328],"Jing":[329],"Li,":[330],"Charles":[331],"E.":[332],"Dowling,":[333],"Eugenia":[334],"V.":[335],"Broude,":[336],"Igor":[337],"B.":[338],"Roninson,":[339],"Campbell":[340],"McInnes,":[341],"Mengqian":[342],"Chen.":[343],"degraders":[345],"CDK8/CDK19":[347],"potently":[350],"myeloma":[353],"proliferation.":[354],"[abstract].":[355],"In:":[356],"Proceedings":[357],"American":[360],"Association":[361],"Research":[364],"Annual":[365],"Meeting":[366],"2023;":[367],"Part":[368],"1":[369],"(Regular":[370],"Invited":[372],"Abstracts);":[373],"2023":[374],"Apr":[375],"14-19;":[376],"Orlando,":[377],"FL.":[378],"Philadelphia":[379],"(PA):":[380],"AACR;":[381],"Res":[383],"2023;83(7_Suppl):Abstract":[384],"nr":[385],"5018.":[386]},"counts_by_year":[{"year":2025,"cited_by_count":1}],"updated_date":"2026-10-14T16:39:01.820549","created_date":"2023-06-10T00:00:00"}
