{"id":"https://openalex.org/W2503510513","doi":"https://doi.org/10.1158/1538-7445.am2016-2823","title":"Abstract 2823: Identification of highly selective inhibitors of cyclin-dependent kinase 12","display_name":"Abstract 2823: Identification of highly selective inhibitors of cyclin-dependent kinase 12","publication_year":2016,"publication_date":"2016-07-15","ids":{"openalex":"https://openalex.org/W2503510513","doi":"https://doi.org/10.1158/1538-7445.am2016-2823","mag":"2503510513"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2016-2823","doi":"https://doi.org/10.1158/1538-7445.am2016-2823","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2016-2823","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/A5090413812","display_name":"Axel Choidas","orcid":"https://orcid.org/0000-0003-2132-4939","observed_orcids":["https://orcid.org/0000-0003-2132-4939"]},"institutions":[{"id":"https://openalex.org/I4210120403","display_name":"Lead Discovery Center (Germany)","ror":"https://ror.org/02jy4mx12","country_code":"DE","type":"company","lineage":["https://openalex.org/I4210120403"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Axel Choidas","raw_affiliation_strings":["1Lead Discovery Center GmbH, Dortmund, Germany;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Lead Discovery Center GmbH, Dortmund, Germany;","institution_ids":["https://openalex.org/I4210120403"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5052263137","display_name":"Carsten Schultz\u2010Fademrecht","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210120403","display_name":"Lead Discovery Center (Germany)","ror":"https://ror.org/02jy4mx12","country_code":"DE","type":"company","lineage":["https://openalex.org/I4210120403"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Carsten Schultz-Fademrecht","raw_affiliation_strings":["1Lead Discovery Center GmbH, Dortmund, Germany;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Lead Discovery Center GmbH, Dortmund, Germany;","institution_ids":["https://openalex.org/I4210120403"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046967082","display_name":"Carsten Degeenhardt","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210120403","display_name":"Lead Discovery Center (Germany)","ror":"https://ror.org/02jy4mx12","country_code":"DE","type":"company","lineage":["https://openalex.org/I4210120403"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Carsten Degeenhardt","raw_affiliation_strings":["1Lead Discovery Center GmbH, Dortmund, Germany;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Lead Discovery Center GmbH, Dortmund, Germany;","institution_ids":["https://openalex.org/I4210120403"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5014718611","display_name":"Peter Habenberger","orcid":"https://orcid.org/0000-0002-1251-264X","observed_orcids":["https://orcid.org/0000-0002-1251-264X"]},"institutions":[{"id":"https://openalex.org/I4210120403","display_name":"Lead Discovery Center (Germany)","ror":"https://ror.org/02jy4mx12","country_code":"DE","type":"company","lineage":["https://openalex.org/I4210120403"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Peter Habenberger","raw_affiliation_strings":["1Lead Discovery Center GmbH, Dortmund, Germany;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Lead Discovery Center GmbH, Dortmund, Germany;","institution_ids":["https://openalex.org/I4210120403"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Uwe Koch","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210120403","display_name":"Lead Discovery Center (Germany)","ror":"https://ror.org/02jy4mx12","country_code":"DE","type":"company","lineage":["https://openalex.org/I4210120403"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Uwe Koch","raw_affiliation_strings":["1Lead Discovery Center GmbH, Dortmund, Germany;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Lead Discovery Center GmbH, Dortmund, Germany;","institution_ids":["https://openalex.org/I4210120403"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5077558723","display_name":"Jan Eickhoff","orcid":"https://orcid.org/0000-0002-5537-438X","observed_orcids":["https://orcid.org/0000-0002-5537-438X"]},"institutions":[{"id":"https://openalex.org/I4210120403","display_name":"Lead Discovery Center (Germany)","ror":"https://ror.org/02jy4mx12","country_code":"DE","type":"company","lineage":["https://openalex.org/I4210120403"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Jan E. Eickhoff","raw_affiliation_strings":["1Lead Discovery Center GmbH, Dortmund, Germany;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Lead Discovery Center GmbH, Dortmund, Germany;","institution_ids":["https://openalex.org/I4210120403"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5048688857","display_name":"Ann Katrin Greifenberg","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I135140700","display_name":"University of Bonn","ror":"https://ror.org/041nas322","country_code":"DE","type":"education","lineage":["https://openalex.org/I135140700"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Ann Kathrin Greifenberg","raw_affiliation_strings":["2Research Center Caesar & University of Bonn, Bonn, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Research Center Caesar & University of Bonn, Bonn, Germany","institution_ids":["https://openalex.org/I135140700"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5103171217","display_name":"Peter Nu\u00dfbaumer","orcid":"https://orcid.org/0000-0002-2761-629X","observed_orcids":["https://orcid.org/0000-0002-2761-629X"]},"institutions":[{"id":"https://openalex.org/I4210120403","display_name":"Lead Discovery Center (Germany)","ror":"https://ror.org/02jy4mx12","country_code":"DE","type":"company","lineage":["https://openalex.org/I4210120403"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Peter Nussbaumer","raw_affiliation_strings":["1Lead Discovery Center GmbH, Dortmund, Germany;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Lead Discovery Center GmbH, Dortmund, Germany;","institution_ids":["https://openalex.org/I4210120403"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5068603027","display_name":"Matthias Geyer","orcid":"https://orcid.org/0000-0002-7718-5002","observed_orcids":["https://orcid.org/0000-0002-7718-5002"]},"institutions":[{"id":"https://openalex.org/I135140700","display_name":"University of Bonn","ror":"https://ror.org/041nas322","country_code":"DE","type":"education","lineage":["https://openalex.org/I135140700"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Matthias Geyer","raw_affiliation_strings":["2Research Center Caesar & University of Bonn, Bonn, Germany"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Research Center Caesar & University of Bonn, Bonn, Germany","institution_ids":["https://openalex.org/I135140700"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5009093201","display_name":"Bert Klebl","orcid":"https://orcid.org/0000-0001-5475-9053","observed_orcids":["https://orcid.org/0000-0001-5475-9053"]},"institutions":[{"id":"https://openalex.org/I4210120403","display_name":"Lead Discovery Center (Germany)","ror":"https://ror.org/02jy4mx12","country_code":"DE","type":"company","lineage":["https://openalex.org/I4210120403"]}],"countries":["DE"],"is_corresponding":false,"raw_author_name":"Bert M. Klebl","raw_affiliation_strings":["1Lead Discovery Center GmbH, Dortmund, Germany;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Lead Discovery Center GmbH, Dortmund, Germany;","institution_ids":["https://openalex.org/I4210120403"]}]}],"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":"76","issue":"14_Supplement","first_page":"2823","last_page":"2823"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10274","display_name":"Synthesis and biological activity","score":0.3571999967098236,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T10274","display_name":"Synthesis and biological activity","score":0.3571999967098236,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":0.20280000567436218,"subfield":{"id":"https://openalex.org/subfields/1703","display_name":"Computational Theory and Mathematics"},"field":{"id":"https://openalex.org/fields/17","display_name":"Computer Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T13779","display_name":"Cancer Mechanisms and Therapy","score":0.06109999865293503,"subfield":{"id":"https://openalex.org/subfields/2734","display_name":"Pathology and Forensic 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/cdk12","display_name":"CDK12","score":0.8360000252723694},{"id":"https://openalex.org/keywords/cdk13","display_name":"CDK13","score":0.984000027179718},{"id":"https://openalex.org/keywords/cyclin-dependent-kinase-inhibitors","display_name":"cyclin-dependent kinase inhibitors","score":0.9390000104904175},{"id":"https://openalex.org/keywords/selective-kinase-inhibitors","display_name":"selective kinase inhibitors","score":0.7179999947547913},{"id":"https://openalex.org/keywords/rna-polymerase-ii-c-terminal-domain-phosphorylation","display_name":"RNA polymerase II C-terminal domain phosphorylation","score":0.902999997138977},{"id":"https://openalex.org/keywords/dna-repair","display_name":"DNA repair","score":0.7360000014305115},{"id":"https://openalex.org/keywords/high-grade-serous-ovarian-carcinoma","display_name":"high-grade serous ovarian cancer","score":0.953000009059906},{"id":"https://openalex.org/keywords/structure-based-optimization","display_name":"structure-guided optimization","score":0.8209999799728394},{"id":"https://openalex.org/keywords/anticancer-drug-development","display_name":"anticancer drug development","score":0.49799999594688416},{"id":"https://openalex.org/keywords/cell-cycle-regulation","display_name":"cell cycle regulation","score":0.4959999918937683},{"id":"https://openalex.org/keywords/cdk7","display_name":"CDK7","score":0.42800000309944153},{"id":"https://openalex.org/keywords/cdk8","display_name":"CDK8","score":0.8579999804496765},{"id":"https://openalex.org/keywords/cdk9","display_name":"CDK9","score":0.9990000128746033}],"concepts":[{"id":"https://openalex.org/C124320809","wikidata":"https://www.wikidata.org/wiki/Q46292","display_name":"Cyclin-dependent kinase","level":4,"score":0.9625790119171143},{"id":"https://openalex.org/C199649820","wikidata":"https://www.wikidata.org/wiki/Q14911762","display_name":"Cyclin-dependent kinase 6","level":5,"score":0.6453312039375305},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.6090519428253174},{"id":"https://openalex.org/C94734110","wikidata":"https://www.wikidata.org/wiki/Q18021240","display_name":"Cyclin-dependent kinase 7","level":5,"score":0.5406936407089233},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4980323314666748},{"id":"https://openalex.org/C2778298596","wikidata":"https://www.wikidata.org/wiki/Q17143494","display_name":"CDK inhibitor","level":5,"score":0.47736406326293945},{"id":"https://openalex.org/C120504264","wikidata":"https://www.wikidata.org/wiki/Q1147372","display_name":"Cyclin-dependent kinase 1","level":4,"score":0.4278073310852051},{"id":"https://openalex.org/C29537977","wikidata":"https://www.wikidata.org/wiki/Q188941","display_name":"Cell cycle","level":3,"score":0.3801787793636322},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.368594765663147},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3420538902282715},{"id":"https://openalex.org/C82495950","wikidata":"https://www.wikidata.org/wiki/Q14911732","display_name":"Cyclin-dependent kinase 2","level":4,"score":0.3385559916496277},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.32832014560699463},{"id":"https://openalex.org/C97029542","wikidata":"https://www.wikidata.org/wiki/Q281417","display_name":"Protein kinase A","level":3,"score":0.17181545495986938},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.15678110718727112}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2016-2823","doi":"https://doi.org/10.1158/1538-7445.am2016-2823","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2016-2823","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":[{"score":0.9391000270843506,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[{"score":0.8399999737739563,"display_name":"Good health and well-being","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/W1963547267","https://openalex.org/W2125546783","https://openalex.org/W2409896451","https://openalex.org/W2106498847","https://openalex.org/W2409264133","https://openalex.org/W2994492843","https://openalex.org/W2035369088","https://openalex.org/W2138852914","https://openalex.org/W2092003347","https://openalex.org/W2419027605"],"abstract_inverted_index":{"Abstract":[0],"CDK12":[1,30,93,112,180,214,221,234,261,269,283],"and":[2,19,31,66,88,102,126,158,181,244],"CDK13":[3,182],"belong":[4],"to":[5,82,94,106,135,151,163,253],"the":[6,39,120,161,164,249,256,345,350],"cyclin-dependent":[7,338],"kinase":[8,194,339],"(CDK)":[9],"family,":[10],"which":[11],"includes":[12],"at":[13],"least":[14],"20":[15],"different":[16],"human":[17],"CDKs":[18,25,51,77,125],"CDK-like":[20],"enzymes.":[21],"One":[22],"subclass":[23],"of":[24,38,42,50,123,166,179,198,218,268,275,281,333,337,344,349],"(e.g.":[26,61],"CDK7,":[27],"CDK8,":[28],"CDK9,":[29],"CDK13)":[32],"preferentially":[33],"regulates":[34],"transcription":[35],"by":[36,288],"phosphorylation":[37,271],"C-terminal":[40],"domain":[41],"RNA":[43,276],"polymerase":[44,277],"II":[45],"(RNAPII),":[46],"whereas":[47],"another":[48],"subgroup":[49],"plays":[52],"a":[53,113,185,192],"pivotal":[54,121],"role":[55,122],"in":[56,85,97,145,155,302,303],"controlling":[57],"cell":[58,71],"cycle":[59,72],"progression":[60],"CDK1,":[62],"CDK2,":[63],"CDK4,":[64],"CDK6":[65],"CDK7).":[67],"Both":[68],"groups":[69],"-":[70,78],"as":[73,75,273],"well":[74],"transcriptional":[76],"have":[79,236,264],"been":[80],"reported":[81],"be":[83,95,254,300],"involved":[84,96],"cancer":[86,305],"development":[87],"progression.":[89],"Recent":[90],"reports":[91],"indicated":[92],"DNA":[98],"damage":[99],"repair":[100],"mechanisms":[101],"linked":[103],"its":[104],"mutation":[105],"high-grade":[107],"serous":[108],"ovarian":[109],"carcinoma":[110],"rendering":[111],"promising":[114,239],"target":[115,250],"for":[116,131,353],"drug":[117,187],"development.":[118],"However,":[119],"individual":[124],"their":[127],"complex":[128],"regulation":[129],"requests":[130],"highly":[132,334],"selective":[133,167,174,233,260,335],"inhibitors":[134,178,222,235,284,336],"avoid":[136],"unwanted":[137],"adverse":[138],"effects.":[139],"Non-specific":[140],"first-generation":[141],"CDK-inhibitors":[142],"cause":[143],"toxicity":[144],"vivo":[146,304],"issues.":[147],"They":[148],"showed":[149],"little":[150],"no":[152],"therapeutic":[153],"window":[154],"clinical":[156],"trials":[157],"thus":[159],"shifted":[160],"focus":[162],"optimization":[165,211],"small":[168,175],"molecule":[169],"CDK":[170,229],"inhibitors.":[171,215],"To":[172],"identify":[173],"molecular":[176],"weight":[177],"we":[183],"employed":[184],"rationale":[186],"discovery":[188],"approach":[189],"based":[190,210],"on":[191,248],"focused":[193],"library":[195],"screen.":[196],"Screening":[197],"slightly":[199],"over":[200],"16.000":[201],"compounds":[202],"identified":[203],"several":[204],"hit":[205],"compound":[206],"classes.":[207],"Medicinal":[208],"chemistry":[209],"yielded":[212],"nanomolar":[213],"The":[216,294],"selectivity":[217],"these":[219,282],"improved":[220,287],"is":[223,285],"excellent,":[224],"when":[225],"tested":[226,301],"against":[227],"12":[228],"family":[230,263],"members.":[231],"Such":[232],"also":[237],"shown":[238,265],"physicochemical":[240],"properties,":[241],"indicating":[242],"lead-":[243],"drug-likeness.":[245],"Although,":[246],"potency":[247,280],"still":[251],"needs":[252],"improved,":[255],"frontrunners":[257],"from":[258],"our":[259],"inhibitor":[262],"cellular":[266],"inhibition":[267],"substrate":[270],"such":[272],"those":[274],"II.":[278],"Currently,":[279],"being":[286],"using":[289],"structure-guided":[290],"medicinal":[291],"chemistry-based":[292],"optimization.":[293],"resulting":[295],"lead":[296],"candidates":[297],"will":[298],"then":[299],"models.":[306],"Citation":[307],"Format:":[308],"Axel":[309],"Choidas,":[310],"Carsten":[311,313],"Schultz-Fademrecht,":[312],"Degeenhardt,":[314],"Peter":[315,325],"Habenberger,":[316],"Uwe":[317],"Koch,":[318],"Jan":[319],"E.":[320],"Eickhoff,":[321],"Ann":[322],"Kathrin":[323],"Greifenberg,":[324],"Nussbaumer,":[326],"Matthias":[327],"Geyer,":[328],"Bert":[329],"M.":[330],"Klebl.":[331],"Identification":[332],"12.":[340],"[abstract].":[341],"In:":[342],"Proceedings":[343],"107th":[346],"Annual":[347],"Meeting":[348],"American":[351],"Association":[352],"Cancer":[354,365],"Research;":[355],"2016":[356],"Apr":[357],"16-20;":[358],"New":[359],"Orleans,":[360],"LA.":[361],"Philadelphia":[362],"(PA):":[363],"AACR;":[364],"Res":[366],"2016;76(14":[367],"Suppl):Abstract":[368],"nr":[369],"2823.":[370]},"counts_by_year":[{"year":2016,"cited_by_count":1}],"updated_date":"2026-10-11T09:32:39.932853","created_date":"2025-10-10T00:00:00"}
