{"id":"https://openalex.org/W4390761622","doi":"https://doi.org/10.1158/1538-7445.dnarepair24-a004","title":"Abstract A004: Targeting tumor hypoxia with prodrugs of DNA-dependent protein kinase inhibitors","display_name":"Abstract A004: Targeting tumor hypoxia with prodrugs of DNA-dependent protein kinase inhibitors","publication_year":2024,"publication_date":"2024-01-09","ids":{"openalex":"https://openalex.org/W4390761622","doi":"https://doi.org/10.1158/1538-7445.dnarepair24-a004"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.dnarepair24-a004","doi":"https://doi.org/10.1158/1538-7445.dnarepair24-a004","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.dnarepair24-a004","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","is_traditional":false,"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/A5090643688","display_name":"Lydia P. Liew","orcid":"https://orcid.org/0000-0002-9322-2010","observed_orcids":["https://orcid.org/0000-0002-9322-2010"]},"institutions":[{"id":"https://openalex.org/I154130895","display_name":"University of Auckland","ror":"https://ror.org/03b94tp07","country_code":"NZ","type":"education","lineage":["https://openalex.org/I154130895"]}],"countries":["NZ"],"is_corresponding":false,"raw_author_name":"Lydia P. Liew","raw_affiliation_strings":["1University of Auckland, Auckland, New Zealand,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Auckland, Auckland, New Zealand,","institution_ids":["https://openalex.org/I154130895"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5017270961","display_name":"Cho Rong Hong","orcid":"https://orcid.org/0000-0002-4304-1764","observed_orcids":["https://orcid.org/0000-0002-4304-1764"]},"institutions":[{"id":"https://openalex.org/I154130895","display_name":"University of Auckland","ror":"https://ror.org/03b94tp07","country_code":"NZ","type":"education","lineage":["https://openalex.org/I154130895"]}],"countries":["NZ"],"is_corresponding":false,"raw_author_name":"Cho R. Hong","raw_affiliation_strings":["1University of Auckland, Auckland, New Zealand,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Auckland, Auckland, New Zealand,","institution_ids":["https://openalex.org/I154130895"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5065301832","display_name":"Benjamin D. Dickson","orcid":"https://orcid.org/0000-0001-6860-903X","observed_orcids":["https://orcid.org/0000-0001-6860-903X"]},"institutions":[{"id":"https://openalex.org/I52179390","display_name":"University of Waikato","ror":"https://ror.org/013fsnh78","country_code":"NZ","type":"education","lineage":["https://openalex.org/I52179390"]}],"countries":["NZ"],"is_corresponding":false,"raw_author_name":"Benjamin D. Dickson","raw_affiliation_strings":["2University of Waikato, Hamilton, New Zealand"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2University of Waikato, Hamilton, New Zealand","institution_ids":["https://openalex.org/I52179390"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5113289545","display_name":"Way Wua Wong","orcid":"https://orcid.org/0000-0002-2300-0930","observed_orcids":["https://orcid.org/0000-0002-2300-0930"]},"institutions":[{"id":"https://openalex.org/I154130895","display_name":"University of Auckland","ror":"https://ror.org/03b94tp07","country_code":"NZ","type":"education","lineage":["https://openalex.org/I154130895"]}],"countries":["NZ"],"is_corresponding":false,"raw_author_name":"Way W. Wong","raw_affiliation_strings":["1University of Auckland, Auckland, New Zealand,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Auckland, Auckland, New Zealand,","institution_ids":["https://openalex.org/I154130895"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5078146193","display_name":"Stephen M. F. Jamieson","orcid":"https://orcid.org/0000-0002-5485-9211","observed_orcids":["https://orcid.org/0000-0002-5485-9211"]},"institutions":[{"id":"https://openalex.org/I154130895","display_name":"University of Auckland","ror":"https://ror.org/03b94tp07","country_code":"NZ","type":"education","lineage":["https://openalex.org/I154130895"]}],"countries":["NZ"],"is_corresponding":false,"raw_author_name":"Stephen M. Jamieson","raw_affiliation_strings":["1University of Auckland, Auckland, New Zealand,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Auckland, Auckland, New Zealand,","institution_ids":["https://openalex.org/I154130895"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5087508568","display_name":"William Robert Wilson","orcid":"https://orcid.org/0000-0002-9939-8738","observed_orcids":["https://orcid.org/0000-0002-9939-8738"]},"institutions":[{"id":"https://openalex.org/I154130895","display_name":"University of Auckland","ror":"https://ror.org/03b94tp07","country_code":"NZ","type":"education","lineage":["https://openalex.org/I154130895"]}],"countries":["NZ"],"is_corresponding":false,"raw_author_name":"William R Wilson","raw_affiliation_strings":["1University of Auckland, Auckland, New Zealand,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Auckland, Auckland, New Zealand,","institution_ids":["https://openalex.org/I154130895"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5067234230","display_name":"Michael P. Hay","orcid":"https://orcid.org/0000-0002-7087-9087","observed_orcids":["https://orcid.org/0000-0002-7087-9087"]},"institutions":[{"id":"https://openalex.org/I154130895","display_name":"University of Auckland","ror":"https://ror.org/03b94tp07","country_code":"NZ","type":"education","lineage":["https://openalex.org/I154130895"]}],"countries":["NZ"],"is_corresponding":false,"raw_author_name":"Michael P. Hay","raw_affiliation_strings":["1University of Auckland, Auckland, New Zealand,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of Auckland, Auckland, New Zealand,","institution_ids":["https://openalex.org/I154130895"]}]}],"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":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"84","issue":"1_Supplement","first_page":"A004","last_page":"A004"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11176","display_name":"Radiation Therapy and Dosimetry","score":0.5605000257492065,"subfield":{"id":"https://openalex.org/subfields/3108","display_name":"Radiation"},"field":{"id":"https://openalex.org/fields/31","display_name":"Physics and Astronomy"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},"topics":[{"id":"https://openalex.org/T11176","display_name":"Radiation Therapy and Dosimetry","score":0.5605000257492065,"subfield":{"id":"https://openalex.org/subfields/3108","display_name":"Radiation"},"field":{"id":"https://openalex.org/fields/31","display_name":"Physics and Astronomy"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10631","display_name":"Cancer, Hypoxia, and Metabolism","score":0.17800000309944153,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"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/T12356","display_name":"Bioactive Compounds and Antitumor Agents","score":0.07569999992847443,"subfield":{"id":"https://openalex.org/subfields/3005","display_name":"Toxicology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/tumor-hypoxia","display_name":"tumor hypoxia","score":0.9800000190734863},{"id":"https://openalex.org/keywords/hypoxia-activated-prodrug","display_name":"hypoxia-activated prodrug","score":0.9700000286102295},{"id":"https://openalex.org/keywords/radiosensitization","display_name":"radiosensitization","score":0.9700000286102295},{"id":"https://openalex.org/keywords/non-homologous-end-joining","display_name":"non-homologous end joining","score":0.9200000166893005},{"id":"https://openalex.org/keywords/double-strand-break-repair","display_name":"DNA double-strand break repair","score":0.9079999923706055},{"id":"https://openalex.org/keywords/carbamate-linker","display_name":"carbamate linker","score":0.8600000143051147},{"id":"https://openalex.org/keywords/prkdc","display_name":"PRKDC","score":0.6679999828338623},{"id":"https://openalex.org/keywords/tumor-xenografts","display_name":"tumor xenografts","score":0.7269999980926514},{"id":"https://openalex.org/keywords/tumor-selectivity","display_name":"tumor selectivity","score":0.49300000071525574}],"concepts":[{"id":"https://openalex.org/C108215921","wikidata":"https://www.wikidata.org/wiki/Q603741","display_name":"Prodrug","level":2,"score":0.6959229707717896},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.5568686723709106},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5425769090652466},{"id":"https://openalex.org/C58962609","wikidata":"https://www.wikidata.org/wiki/Q2353022","display_name":"Radioresistance","level":3,"score":0.4822038412094116},{"id":"https://openalex.org/C143425029","wikidata":"https://www.wikidata.org/wiki/Q5205747","display_name":"DNA damage","level":3,"score":0.4725850820541382},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.4621475636959076},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.44440746307373047},{"id":"https://openalex.org/C96232424","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell","level":3,"score":0.43975770473480225},{"id":"https://openalex.org/C2781305896","wikidata":"https://www.wikidata.org/wiki/Q6875874","display_name":"Misonidazole","level":3,"score":0.4220907390117645},{"id":"https://openalex.org/C2776107976","wikidata":"https://www.wikidata.org/wiki/Q1786433","display_name":"Tumor microenvironment","level":3,"score":0.42052358388900757},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.40727031230926514},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.3607364296913147},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3586059510707855},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.3526068329811096},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.23658910393714905},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.2053769826889038},{"id":"https://openalex.org/C3020616263","wikidata":"https://www.wikidata.org/wiki/Q1216998","display_name":"Tumor cells","level":2,"score":0.08137020468711853},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.07706072926521301}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.dnarepair24-a004","doi":"https://doi.org/10.1158/1538-7445.dnarepair24-a004","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.dnarepair24-a004","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"}],"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/W3152832865","https://openalex.org/W7066179355","https://openalex.org/W3097115020","https://openalex.org/W2339184074","https://openalex.org/W2973828379","https://openalex.org/W7055362271","https://openalex.org/W2785724953","https://openalex.org/W7128956924","https://openalex.org/W2345081105","https://openalex.org/W4390729907"],"abstract_inverted_index":{"Abstract":[0],"Radiation":[1],"therapy":[2],"kills":[3],"cancer":[4],"cells":[5,117,155,171,216,281],"through":[6,26,118,224],"the":[7,38,79,103,107,164,244,291,360,403],"generation":[8,358],"of":[9,31,44,58,105,128,161,202,248,279,302,321,329,353,359,394,402],"DNA":[10,410],"double-strand":[11],"breaks":[12],"(DSB)":[13],"which":[14],"give":[15],"rise":[16],"to":[17,74,84,199,217,254,416],"lethal":[18],"chromosome":[19],"aberrations.":[20],"Intrinsic":[21],"radiation":[22,80],"resistance":[23],"is":[24,54,61,95,325],"mediated":[25],"several":[27],"mechanisms":[28],"including":[29],"suppression":[30],"initial":[32,138],"DSB":[33,45],"formation":[34],"by":[35,46,335],"hypoxia":[36,83,391],"in":[37,93,146,173,214,220,228,237,250,288,308,344,407],"tumor":[39,66,100,116,177,226,330,364,390],"microenvironment":[40],"and":[41,60,112,148,168,175,187,196,232,285,305,331,339],"rapid":[42],"repair":[43],"non-homologous":[47],"end-joining":[48],"(NHEJ).":[49],"DNA-dependent":[50,395],"protein":[51,396],"kinase":[52,397],"(DNA-PK)":[53],"a":[55,62,119,125,265,350],"key":[56],"element":[57],"NHEJ":[59],"well-validated":[63],"target":[64],"for":[65,98],"radiosensitization.":[67],"However,":[68,243],"DNA-PK":[69,86,129,144,165,197,204,267,342,361],"inhibition":[70,145],"has":[71],"been":[72],"demonstrated":[73],"radiosensitize":[75],"normal":[76,332],"tissues":[77],"within":[78],"field.":[81],"Exploiting":[82],"release":[85],"inhibitors":[87,343,398],"from":[88],"hypoxia-activated":[89],"prodrugs":[90,393],"(HAPs)":[91],"selectively":[92,213],"tumors":[94,236,307],"one":[96],"strategy":[97],"enhancing":[99],"selectivity,":[101],"with":[102,257,392],"advantage":[104],"sensitizing":[106,114],"most":[108],"radioresistant":[109],"(hypoxic)":[110],"subpopulation":[111],"potentially":[113],"oxic":[115,284],"bystander":[120],"effect.":[121],"We":[122,179],"recently":[123],"discovered":[124],"new":[126],"class":[127],"inhibitor":[130,362],"based":[131],"on":[132,270],"an":[133,158,258,313],"imidazo[4,5-c]":[134],"pyridine-2-one":[135],"scaffold.":[136],"Our":[137],"lead,":[139],"SN39536,":[140],"provided":[141,276,299],"highly":[142],"selective":[143],"biochemical":[147],"cell-based":[149],"assays,":[150],"potently":[151],"radiosensitized":[152,169,234],"parental":[153],"HAP1":[154],"but":[156],"not":[157],"isogenic":[159],"knockout":[160],"PRKDC":[162],"(encoding":[163],"catalytic":[166],"subunit),":[167],"HCT116":[170,235,280,304],"both":[172,283,303],"vitro":[174],"as":[176],"xenografts.":[178],"explored":[180],"three":[181],"prodrug":[182,262,322],"linker":[183],"approaches":[184],"(carbamate,":[185],"ether,":[186],"quaternary":[188],"ammonium":[189],"salt":[190],"linkers":[191],"between":[192],"nitroimidazole":[193],"trigger":[194],"units":[195],"inhibitors)":[198],"prepare":[200],"HAPs":[201,256,338],"various":[203],"inhibitors.":[205],"The":[206],"2-nitroimidazole":[207],"carbamate":[208],"HAP,":[209,292],"SN39884,":[210],"was":[211],"metabolized":[212],"hypoxic":[215,225,273,286,296],"generate":[218],"SN39536":[219],"vitro,":[221,289],"efficiently":[222],"penetrated":[223],"tissue":[227,333],"multicellular":[229],"layer":[230],"cultures,":[231],"significantly":[233],"NIH-III":[238,309],"mice":[239,251],"at":[240],"well-tolerated":[241],"doses.":[242],"limited":[245],"metabolic":[246,323],"stability":[247,324],"SN39884":[249],"led":[252],"us":[253],"explore":[255],"ether":[259],"linker.":[260],"Ether":[261],"SN40458":[263,298],"released":[264],"phenolic":[266],"inhibitor,":[268],"SN39872,":[269],"reduction":[271],"under":[272,282],"conditions.":[274],"SN39872":[275],"robust":[277],"sensitization":[278],"conditions":[287],"while":[290],"SN40458,":[293],"only":[294],"sensitized":[295],"cells.":[297],"significant":[300],"radiosensitization":[301,334],"UT-SCC-74B":[306],"mice,":[310],"measured":[311],"using":[312],"ex":[314],"vivo":[315],"clonogenic":[316],"survival":[317],"assay.":[318],"Further":[319],"optimization":[320],"required":[326],"before":[327],"comparison":[328,347],"these":[336],"second-generation":[337],"their":[340],"corresponding":[341],"mice.":[345],"This":[346],"will":[348],"provide":[349],"critical":[351],"test":[352],"our":[354],"hypothesis":[355],"that":[356],"hypoxia-dependent":[357],"enhances":[363],"selectivity.":[365],"Citation":[366],"Format:":[367],"Lydia":[368],"P.":[369,387],"Liew,":[370],"Cho":[371],"R.":[372],"Hong,":[373],"Benjamin":[374],"D.":[375],"Dickson,":[376],"Way":[377],"W.":[378],"Wong,":[379],"Stephen":[380],"M.":[381],"Jamieson,":[382],"William":[383],"R":[384],"Wilson,":[385],"Michael":[386],"Hay.":[388],"Targeting":[389],"[abstract].":[399],"In:":[400],"Proceedings":[401],"AACR":[404],"Special":[405],"Conference":[406],"Cancer":[408,428],"Research:":[409],"Damage":[411],"Repair:":[412],"From":[413],"Basic":[414],"Science":[415],"Future":[417],"Clinical":[418],"Application;":[419],"2024":[420],"Jan":[421],"9-11;":[422],"Washington,":[423],"DC.":[424],"Philadelphia":[425],"(PA):":[426],"AACR;":[427],"Res":[429],"2024;84(1":[430],"Suppl):Abstract":[431],"nr":[432],"A004.":[433]},"counts_by_year":[],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2024-01-13T00:00:00"}