{"id":"https://openalex.org/W4392701142","doi":"https://doi.org/10.1158/1535-7163.c.6543945.v1","title":"Data from An Enzymatically Cleavable Tripeptide Linker for Maximizing the Therapeutic Index of Antibody\u2013Drug Conjugates","display_name":"Data from An Enzymatically Cleavable Tripeptide Linker for Maximizing the Therapeutic Index of Antibody\u2013Drug Conjugates","publication_year":2023,"publication_date":"2023-04-03","ids":{"openalex":"https://openalex.org/W4392701142","doi":"https://doi.org/10.1158/1535-7163.c.6543945.v1"},"language":"en","primary_location":{"id":"doi:10.1158/1535-7163.c.6543945.v1","doi":"https://doi.org/10.1158/1535-7163.c.6543945.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1535-7163.c.6543945.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"volume":null,"type":"other","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.1158/1535-7163.c.6543945.v1","any_repository_has_fulltext":null},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5003763671","display_name":"Summer Y.Y. Ha","orcid":"https://orcid.org/0000-0002-5297-3686","observed_orcids":["https://orcid.org/0000-0002-5297-3686"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Summer Y.Y. Ha","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-5297-3686","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5069745826","display_name":"Yasuaki Anami","orcid":"https://orcid.org/0000-0001-5136-7708","observed_orcids":["https://orcid.org/0000-0001-5136-7708"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Yasuaki Anami","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0001-5136-7708","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5063974451","display_name":"Chisato M. Yamazaki","orcid":"https://orcid.org/0000-0002-0785-7352","observed_orcids":["https://orcid.org/0000-0002-0785-7352"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Chisato M. Yamazaki","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-0785-7352","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036408326","display_name":"Wei Xiong","orcid":"https://orcid.org/0000-0003-2624-6474","observed_orcids":["https://orcid.org/0000-0003-2624-6474"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Wei Xiong","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0003-2624-6474","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5059322556","display_name":"Candice M. Haase","orcid":"https://orcid.org/0000-0001-5136-5817","observed_orcids":["https://orcid.org/0000-0001-5136-5817"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Candice M. Haase","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0001-5136-5817","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5014998467","display_name":"Scott D. Olson","orcid":"https://orcid.org/0000-0001-8032-3755","observed_orcids":["https://orcid.org/0000-0001-8032-3755"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Scott D. Olson","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0001-8032-3755","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025672158","display_name":"Jangsoon Lee","orcid":"https://orcid.org/0000-0002-6862-5686","observed_orcids":["https://orcid.org/0000-0002-6862-5686"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jangsoon Lee","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-6862-5686","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5088814426","display_name":"Naoto Tada Ueno","orcid":"https://orcid.org/0000-0002-0166-7275","observed_orcids":["https://orcid.org/0000-0002-0166-7275"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Naoto T. Ueno","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-0166-7275","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100320378","display_name":"Ningyan Zhang","orcid":"https://orcid.org/0000-0002-4348-2180","observed_orcids":["https://orcid.org/0000-0002-4348-2180"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Ningyan Zhang","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-4348-2180","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5026356376","display_name":"Zhiqiang An","orcid":"https://orcid.org/0000-0001-9309-2335","observed_orcids":["https://orcid.org/0000-0001-9309-2335","https://orcid.org/0000-0002-4348-2180"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Zhiqiang An","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0001-9309-2335","affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5022743912","display_name":"Kyoji Tsuchikama","orcid":"https://orcid.org/0000-0002-2359-0408","observed_orcids":["https://orcid.org/0000-0002-2359-0408"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Kyoji Tsuchikama","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-2359-0408","affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"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":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11016","display_name":"Monoclonal and Polyclonal Antibodies Research","score":0.7753999829292297,"subfield":{"id":"https://openalex.org/subfields/2741","display_name":"Radiology, Nuclear Medicine and Imaging"},"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/T11016","display_name":"Monoclonal and Polyclonal Antibodies Research","score":0.7753999829292297,"subfield":{"id":"https://openalex.org/subfields/2741","display_name":"Radiology, Nuclear Medicine and Imaging"},"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/T10063","display_name":"Nanoparticle-Based Drug Delivery","score":0.07429999858140945,"subfield":{"id":"https://openalex.org/subfields/2502","display_name":"Biomaterials"},"field":{"id":"https://openalex.org/fields/25","display_name":"Materials Science"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10911","display_name":"Chemical Synthesis and Analysis","score":0.03849999979138374,"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/antibody-drug-conjugates","display_name":"antibody-drug conjugates","score":0.9900000095367432},{"id":"https://openalex.org/keywords/valine-citrulline-linker","display_name":"valine-citrulline linker","score":0.9390000104904175},{"id":"https://openalex.org/keywords/protease-cleavable-linker","display_name":"protease-cleavable linker","score":0.8169999718666077},{"id":"https://openalex.org/keywords/trastuzumab-emtansine","display_name":"trastuzumab emtansine","score":0.718999981880188},{"id":"https://openalex.org/keywords/trastuzumab-deruxtecan","display_name":"trastuzumab deruxtecan","score":0.9990000128746033},{"id":"https://openalex.org/keywords/hepatotoxicity","display_name":"hepatotoxicity","score":0.7559999823570251},{"id":"https://openalex.org/keywords/neutropenia","display_name":"neutropenia","score":0.7210000157356262},{"id":"https://openalex.org/keywords/therapeutic-index","display_name":"therapeutic index","score":0.8849999904632568},{"id":"https://openalex.org/keywords/antitumor-efficacy","display_name":"antitumor efficacy","score":0.722000002861023},{"id":"https://openalex.org/keywords/xenograft-tumor-model","display_name":"xenograft tumor model","score":0.718999981880188}],"concepts":[{"id":"https://openalex.org/C2780557392","wikidata":"https://www.wikidata.org/wiki/Q523796","display_name":"Linker","level":2,"score":0.7776819467544556},{"id":"https://openalex.org/C197336794","wikidata":"https://www.wikidata.org/wiki/Q5161150","display_name":"Conjugate","level":2,"score":0.7039361596107483},{"id":"https://openalex.org/C19831878","wikidata":"https://www.wikidata.org/wiki/Q659446","display_name":"Therapeutic index","level":3,"score":0.6723545789718628},{"id":"https://openalex.org/C167392928","wikidata":"https://www.wikidata.org/wiki/Q4820777","display_name":"Tripeptide","level":3,"score":0.6455470323562622},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5676842927932739},{"id":"https://openalex.org/C2780035454","wikidata":"https://www.wikidata.org/wiki/Q8386","display_name":"Drug","level":2,"score":0.5544002652168274},{"id":"https://openalex.org/C2777325958","wikidata":"https://www.wikidata.org/wiki/Q1069596","display_name":"Antibody-drug conjugate","level":4,"score":0.46852678060531616},{"id":"https://openalex.org/C159654299","wikidata":"https://www.wikidata.org/wiki/Q79460","display_name":"Antibody","level":2,"score":0.45807573199272156},{"id":"https://openalex.org/C2777382242","wikidata":"https://www.wikidata.org/wiki/Q6017816","display_name":"Index (typography)","level":2,"score":0.441464900970459},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.4325249493122101},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3513273596763611},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3139312267303467},{"id":"https://openalex.org/C2779281246","wikidata":"https://www.wikidata.org/wiki/Q172847","display_name":"Peptide","level":2,"score":0.27864521741867065},{"id":"https://openalex.org/C542903549","wikidata":"https://www.wikidata.org/wiki/Q422248","display_name":"Monoclonal antibody","level":3,"score":0.2760196030139923},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.21801817417144775},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.14182257652282715},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.0941479504108429},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.08538630604743958},{"id":"https://openalex.org/C111919701","wikidata":"https://www.wikidata.org/wiki/Q9135","display_name":"Operating system","level":1,"score":0.0},{"id":"https://openalex.org/C136764020","wikidata":"https://www.wikidata.org/wiki/Q466","display_name":"World Wide Web","level":1,"score":0.0},{"id":"https://openalex.org/C134306372","wikidata":"https://www.wikidata.org/wiki/Q7754","display_name":"Mathematical analysis","level":1,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1535-7163.c.6543945.v1","doi":"https://doi.org/10.1158/1535-7163.c.6543945.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1535-7163.c.6543945.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1158/1535-7163.c.6543945.v1","doi":"https://doi.org/10.1158/1535-7163.c.6543945.v1","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1535-7163.c.6543945.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9789000153541565}],"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/W4284878954","https://openalex.org/W2808751881","https://openalex.org/W4388771441","https://openalex.org/W4402147236","https://openalex.org/W4392688624","https://openalex.org/W3107784614","https://openalex.org/W2548368791","https://openalex.org/W3135311043","https://openalex.org/W7170132303","https://openalex.org/W6982427078"],"abstract_inverted_index":{"Abstract":[0],"Valine\u2013citrulline":[1],"is":[2],"a":[3],"protease-cleavable":[4],"linker":[5,155],"commonly":[6],"used":[7],"in":[8,23,99,133,144],"many":[9],"drug":[10,65,167],"delivery":[11,168],"systems,":[12],"including":[13],"antibody\u2013drug":[14],"conjugates":[15,138],"(ADC)":[16],"for":[17],"cancer":[18],"therapy.":[19],"However,":[20],"its":[21],"suboptimal":[22],"vivo":[24],"stability":[25],"can":[26],"cause":[27],"various":[28],"adverse":[29],"effects":[30],"such":[31],"as":[32],"neutropenia":[33],"and":[34,67,81,96,118,127,130,152,165,176],"hepatotoxicity,":[35],"leading":[36],"to":[37,54],"dose":[38,111],"delays":[39],"or":[40],"treatment":[41],"discontinuation.":[42],"Here,":[43],"we":[44],"report":[45],"that":[46,73],"glutamic":[47],"acid\u2013glycine\u2013citrulline":[48],"(EGCit)":[49],"linkers":[50],"have":[51],"the":[52,61,109,113,160],"potential":[53],"solve":[55],"this":[56],"clinical":[57,171],"issue":[58],"without":[59],"compromising":[60],"ability":[62],"of":[63,94,123,163],"traceless":[64],"release":[66],"ADC":[68,76,89],"therapeutic":[69,161],"efficacy.":[70],"We":[71],"demonstrate":[72],"our":[74,87],"EGCit":[75,137],"resists":[77],"neutrophil":[78],"protease\u2013mediated":[79],"degradation":[80],"spares":[82],"differentiating":[83],"human":[84],"neutrophils.":[85],"Notably,":[86],"anti-HER2":[88,115],"shows":[90],"almost":[91],"no":[92],"sign":[93],"blood":[95],"liver":[97,134],"toxicity":[98],"healthy":[100],"mice":[101],"at":[102,108],"80":[103],"mg":[104],"kg\u22121.":[105],"In":[106],"contrast,":[107],"same":[110],"level,":[112],"FDA-approved":[114],"ADCs":[116,164],"Kadcyla":[117,151],"Enhertu":[119],"show":[120],"increased":[121],"levels":[122],"serum":[124],"alanine":[125],"aminotransferase":[126,129],"aspartate":[128],"morphologic":[131],"changes":[132],"tissues.":[135],"Our":[136],"also":[139],"exert":[140],"greater":[141],"antitumor":[142],"efficacy":[143,175],"multiple":[145],"xenograft":[146],"tumor":[147],"models":[148],"compared":[149],"with":[150,173],"Enhertu.":[153],"This":[154],"technology":[156],"could":[157],"substantially":[158],"broaden":[159],"windows":[162],"other":[166],"agents,":[169],"providing":[170],"options":[172],"improved":[174],"safety.":[177]},"counts_by_year":[],"updated_date":"2026-10-27T15:51:10.671819","created_date":"2024-03-13T00:00:00"}
