{"id":"https://openalex.org/W7225655504","doi":"https://doi.org/10.3389/fimmu.2026.1975588","title":"PARP1 and PD-L1 dual-targeted bifunctional small-molecule inhibitors: a novel strategy for dual immunotherapy of triple-negative breast cancer","display_name":"PARP1 and PD-L1 dual-targeted bifunctional small-molecule inhibitors: a novel strategy for dual immunotherapy of triple-negative breast cancer","publication_year":2026,"publication_date":"2026-11-09","ids":{"openalex":"https://openalex.org/W7225655504","doi":"https://doi.org/10.3389/fimmu.2026.1975588"},"language":"en","primary_location":{"id":"doi:10.3389/fimmu.2026.1975588","doi":"https://doi.org/10.3389/fimmu.2026.1975588","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2026.1975588","pdf_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1975588/pdf","source":{"id":"https://openalex.org/S2595292759","display_name":"Frontiers in Immunology","issn_l":"1664-3224","issn":["1664-3224"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Immunology","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1975588/pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5161359071","display_name":"Jing-Jing Du","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210122157","display_name":"Hubei Polytechnic University","ror":"https://ror.org/01z07eq06","country_code":"CN","type":"education","lineage":["https://openalex.org/I4210122157"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Jing-Jing Du","raw_affiliation_strings":["Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, Hubei Polytechnic University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, Hubei Polytechnic University","institution_ids":["https://openalex.org/I4210122157"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161329278","display_name":"Yixiang Fan","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Yixiang Fan","raw_affiliation_strings":["Hubei Jiangxia Laboratory"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Hubei Jiangxia Laboratory","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161325931","display_name":"Xiaoyan Wu","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Xiaoyan Wu","raw_affiliation_strings":["Hubei Jiangxia Laboratory"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Hubei Jiangxia Laboratory","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5133653960","display_name":"Guang Zeng","orcid":"https://orcid.org/0009-0001-3683-8062","observed_orcids":["https://orcid.org/0009-0001-3683-8062"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Guang Zeng","raw_affiliation_strings":["Hubei Jiangxia Laboratory"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Hubei Jiangxia Laboratory","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5147795936","display_name":"Shengfeng YUAN","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Shengfeng Yuan","raw_affiliation_strings":["Hubei Jiangxia Laboratory"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Hubei Jiangxia Laboratory","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161339412","display_name":"Yangbin Huang","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Yangbin Huang","raw_affiliation_strings":["Hubei Jiangxia Laboratory"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Hubei Jiangxia Laboratory","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5023846352","display_name":"Binbin Cheng","orcid":"https://orcid.org/0000-0003-4894-2454","observed_orcids":["https://orcid.org/0000-0003-4894-2454"]},"institutions":[{"id":"https://openalex.org/I4210122157","display_name":"Hubei Polytechnic University","ror":"https://ror.org/01z07eq06","country_code":"CN","type":"education","lineage":["https://openalex.org/I4210122157"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Binbin Cheng","raw_affiliation_strings":["Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, Hubei Polytechnic University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, Hubei Polytechnic University","institution_ids":["https://openalex.org/I4210122157"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5023846352"],"corresponding_institution_ids":["https://openalex.org/I4210122157"],"apc_list":{"value":3150,"currency":"CHF","value_usd":3801},"apc_paid":{"value":3150,"currency":"CHF","value_usd":3801},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"17","issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.5429999828338623,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"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/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.5429999828338623,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"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/T11914","display_name":"PARP inhibition in cancer therapy","score":0.42239999771118164,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"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/T12534","display_name":"Protein Degradation and Inhibitors","score":0.007000000216066837,"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/parp-1","display_name":"PARP1","score":0.7480000257492065},{"id":"https://openalex.org/keywords/pd-l1","display_name":"PD-L1","score":0.9980000257492065},{"id":"https://openalex.org/keywords/triple-negative-breast-cancer","display_name":"triple-negative breast cancer","score":0.9929999709129333},{"id":"https://openalex.org/keywords/pd-1-pd-l1-axis","display_name":"PD-1/PD-L1 axis","score":0.8960000276565552},{"id":"https://openalex.org/keywords/sp1","display_name":"Sp1","score":0.6869999766349792},{"id":"https://openalex.org/keywords/cancer-immunotherapy","display_name":"cancer immunotherapy","score":0.765999972820282},{"id":"https://openalex.org/keywords/t-cell-function","display_name":"T cell function","score":0.6899999976158142},{"id":"https://openalex.org/keywords/tumor-cell-migration-and-invasion","display_name":"tumor cell migration and invasion","score":0.8949999809265137},{"id":"https://openalex.org/keywords/parp-inhibitors","display_name":"PARP inhibitors","score":0.453000009059906}],"concepts":[{"id":"https://openalex.org/C2779962180","wikidata":"https://www.wikidata.org/wiki/Q7083106","display_name":"Olaparib","level":5,"score":0.7167999744415283},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6195999979972839},{"id":"https://openalex.org/C117262875","wikidata":"https://www.wikidata.org/wiki/Q5135057","display_name":"Clonogenic assay","level":3,"score":0.6122999787330627},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5181000232696533},{"id":"https://openalex.org/C2780443040","wikidata":"https://www.wikidata.org/wiki/Q3737863","display_name":"Bifunctional","level":3,"score":0.5034999847412109},{"id":"https://openalex.org/C2779138821","wikidata":"https://www.wikidata.org/wiki/Q7118227","display_name":"PARP inhibitor","level":5,"score":0.48100000619888306},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.4332999885082245},{"id":"https://openalex.org/C530470458","wikidata":"https://www.wikidata.org/wiki/Q128581","display_name":"Breast cancer","level":3,"score":0.4300000071525574},{"id":"https://openalex.org/C553184892","wikidata":"https://www.wikidata.org/wiki/Q1141429","display_name":"Flow cytometry","level":2,"score":0.41359999775886536},{"id":"https://openalex.org/C2778502085","wikidata":"https://www.wikidata.org/wiki/Q7662767","display_name":"Synthetic lethality","level":4,"score":0.4027999937534332},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.3894999921321869},{"id":"https://openalex.org/C96232424","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell","level":3,"score":0.37630000710487366},{"id":"https://openalex.org/C2778480876","wikidata":"https://www.wikidata.org/wiki/Q21112674","display_name":"PARP1","level":5,"score":0.36419999599456787},{"id":"https://openalex.org/C2776090121","wikidata":"https://www.wikidata.org/wiki/Q193529","display_name":"T cell","level":3,"score":0.33149999380111694},{"id":"https://openalex.org/C182979987","wikidata":"https://www.wikidata.org/wiki/Q3907241","display_name":"Poly ADP ribose polymerase","level":4,"score":0.329800009727478},{"id":"https://openalex.org/C2780674031","wikidata":"https://www.wikidata.org/wiki/Q2012719","display_name":"Cancer immunotherapy","level":4,"score":0.3294999897480011},{"id":"https://openalex.org/C2779013556","wikidata":"https://www.wikidata.org/wiki/Q181876","display_name":"Metastasis","level":3,"score":0.32910001277923584},{"id":"https://openalex.org/C189938988","wikidata":"https://www.wikidata.org/wiki/Q24744925","display_name":"NFAT","level":4,"score":0.32440000772476196},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3237999975681305},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.3203999996185303},{"id":"https://openalex.org/C53345823","wikidata":"https://www.wikidata.org/wiki/Q5531554","display_name":"Gene isoform","level":3,"score":0.31369999051094055},{"id":"https://openalex.org/C161624437","wikidata":"https://www.wikidata.org/wiki/Q1988322","display_name":"Small molecule","level":2,"score":0.31279999017715454},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.28929999470710754},{"id":"https://openalex.org/C109541995","wikidata":"https://www.wikidata.org/wiki/Q1881253","display_name":"MCF-7","level":5,"score":0.2872999906539917},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.28360000252723694},{"id":"https://openalex.org/C174510640","wikidata":"https://www.wikidata.org/wiki/Q489618","display_name":"HEK 293 cells","level":3,"score":0.2635999917984009},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.2605000138282776},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.2533000111579895},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.25130000710487366},{"id":"https://openalex.org/C128972844","wikidata":"https://www.wikidata.org/wiki/Q418722","display_name":"Aptamer","level":2,"score":0.25110000371932983}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.3389/fimmu.2026.1975588","doi":"https://doi.org/10.3389/fimmu.2026.1975588","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2026.1975588","pdf_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1975588/pdf","source":{"id":"https://openalex.org/S2595292759","display_name":"Frontiers in Immunology","issn_l":"1664-3224","issn":["1664-3224"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Immunology","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.3389/fimmu.2026.1975588","doi":"https://doi.org/10.3389/fimmu.2026.1975588","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2026.1975588","pdf_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1975588/pdf","source":{"id":"https://openalex.org/S2595292759","display_name":"Frontiers in Immunology","issn_l":"1664-3224","issn":["1664-3224"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Immunology","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.9537000060081482,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320323265","display_name":"Hubei Polytechnic University","ror":"https://ror.org/01z07eq06"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225655504.pdf","grobid_xml":"https://content.openalex.org/works/W7225655504.grobid-xml"},"referenced_works_count":26,"referenced_works":["https://openalex.org/W2032040083","https://openalex.org/W2802268096","https://openalex.org/W2900248192","https://openalex.org/W2902324525","https://openalex.org/W2909301717","https://openalex.org/W3009188653","https://openalex.org/W3024340066","https://openalex.org/W3130791700","https://openalex.org/W3164262721","https://openalex.org/W3202611673","https://openalex.org/W4295540029","https://openalex.org/W4310424284","https://openalex.org/W4324358744","https://openalex.org/W4385737221","https://openalex.org/W4386498300","https://openalex.org/W4394676345","https://openalex.org/W4404252696","https://openalex.org/W4406569168","https://openalex.org/W4409069484","https://openalex.org/W4409869216","https://openalex.org/W4411348097","https://openalex.org/W4413419968","https://openalex.org/W4415623398","https://openalex.org/W4415952728","https://openalex.org/W7123672551","https://openalex.org/W7163918207"],"related_works":["https://openalex.org/W3217547816","https://openalex.org/W4412418399","https://openalex.org/W7220869239","https://openalex.org/W2963537318","https://openalex.org/W4379162507","https://openalex.org/W3110156846","https://openalex.org/W4387215927","https://openalex.org/W7021382620","https://openalex.org/W3188802726","https://openalex.org/W7223178647"],"abstract_inverted_index":{"Objectives":[0],"Current":[1],"single-agent":[2],"PD-L1":[3,183,249],"immunotherapy":[4],"and":[5,19,37,76,118,158,184,211,218,234,250],"PARP":[6,43,93,133],"inhibitor":[7,247],"combination":[8],"regimens":[9],"have":[10],"several":[11],"drawbacks,":[12],"including":[13],"limited":[14],"response":[15],"rates,":[16],"mismatched":[17],"pharmacokinetics,":[18],"overlapping":[20],"toxicities.":[21],"This":[22],"research":[23],"aims":[24],"to":[25,45,84,97,181],"discover":[26],"novel":[27,267],"bifunctional":[28],"small":[29],"molecules":[30],"that":[31,177,194,227],"simultaneously":[32],"block":[33],"the":[34,109,146,166],"PD-1/PD-L1":[35,77,110],"axis":[36],"PARP1,":[38,185,251],"with":[39,170,252],"prominent":[40],"selectivity":[41],"for":[42,152,265],"subtypes,":[44],"overcome":[46],"bottlenecks":[47],"in":[48,200],"triple-negative":[49,202],"breast":[50,203],"cancer":[51,204,270],"immunotherapy.":[52],"Methods":[53],"Computer-aided":[54],"molecular":[55,60],"docking,":[56],"100":[57],"ns":[58],"all-atom":[59],"dynamics":[61],"simulation,":[62],"homogeneous":[63],"time-resolved":[64],"fluorescence":[65],"(HTRF)":[66],"binding":[67],"assay,":[68],"biolayer":[69],"interferometry":[70],"(BLI),":[71],"differential":[72],"scanning":[73],"fluorimetry":[74],"(DSF),":[75],"NFAT":[78],"reporter":[79],"cell":[80,215,232],"assay":[81],"were":[82],"integrated":[83],"characterize":[85],"dual-target":[86,246],"lead":[87,263],"molecules.":[88],"A":[89],"panel":[90],"of":[91,248],"eight":[92],"isoforms":[94],"was":[95],"tested":[96],"evaluate":[98],"compound":[99],"subtype":[100,255],"selectivity.":[101],"Results":[102],"The":[103],"optimized":[104],"molecule":[105],"SP-1":[106,130,178,195,228,241],"potently":[107],"disrupts":[108],"protein-protein":[111],"interaction":[112],"(IC":[113,124,206],"50":[114,125,150,207],"=":[115,126,208],"630":[116],"nM)":[117],"inhibits":[119],"PARP1":[120,254],"at":[121],"nanomolar":[122],"levels":[123],"13":[127],"nM).":[128],"Notably,":[129],"shows":[131],"excellent":[132],"isoform":[134],"selectivity:":[135],"its":[136],"inhibitory":[137],"potency":[138],"against":[139],"PARP2":[140],"is":[141],"nearly":[142],"18-fold":[143],"weaker.":[144],"At":[145],"same":[147],"time,":[148],"IC":[149],"values":[151],"PARP3,":[153],"PARP5a,":[154],"PARP5b,":[155],"PARP7,":[156],"PARP8,":[157],"PARP10":[159],"all":[160],"exceed":[161],"500":[162],"nM,":[163],"greatly":[164],"reducing":[165],"off-target":[167],"risks":[168],"associated":[169],"pan-PARP":[171],"suppression.":[172],"Orthogonal":[173],"biophysical":[174],"characterizations":[175],"confirm":[176],"directly":[179],"binds":[180],"both":[182],"forming":[186],"stable":[187],"intermolecular":[188],"interactions.":[189],"Cell-based":[190],"functional":[191],"assays":[192,224],"demonstrate":[193],"produces":[196],"robust":[197],"anti-tumor":[198],"effects":[199],"MDA-MB-231":[201],"cells":[205],"1.01":[209],"\u03bcM)":[210],"markedly":[212],"restrains":[213],"tumor":[214],"migration,":[216],"invasion,":[217],"long-term":[219],"clonogenic":[220],"growth.":[221],"Functional":[222],"cellular":[223],"further":[225],"demonstrated":[226],"effectively":[229],"restored":[230],"T":[231,236],"function":[233],"enhanced":[235],"cell-mediated":[237],"tumoricidal":[238],"activity.":[239],"Conclusions":[240],"serves":[242],"as":[243,261],"a":[244,262],"balanced":[245],"potent":[253],"selectivity,":[256],"which":[257],"can":[258],"be":[259],"prioritized":[260],"scaffold":[264],"developing":[266],"dual-functional":[268],"anti-breast":[269],"agents.":[271]},"counts_by_year":[],"updated_date":"2026-11-11T12:16:26.678958","created_date":"2026-11-10T00:00:00"}
