{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:05:45Z","timestamp":1790395545480,"version":"4.1.0"},"reference-count":32,"publisher":"Elsevier BV","issue":"10","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["dmd.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Drug Metabolism and Disposition"],"published-print":{"date-parts":[[2019,10]]},"DOI":"10.1124\/dmd.119.087023","type":"journal-article","created":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T01:29:00Z","timestamp":1564450140000},"page":"1146-1155","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":33,"title":["Exposure-Efficacy Analysis of Antibody-Drug Conjugates Delivering an Excessive Level of Payload to Tissues"],"prefix":"10.1016","volume":"47","author":[{"given":"Donglu","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Dragovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang-Fan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Pillow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack D.","family":"Sadowsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dian","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Polson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Cyrus","family":"Khojasteh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis E.C.A.","family":"Hop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/dmd.119.087023_bib1","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1021\/cr100120f","article-title":"Synthesis of DNA-interactive pyrrolo[2,1-c][1,4]benzodiazepines (PBDs)","volume":"111","author":"Antonow","year":"2011","journal-title":"Chem Rev"},{"issue":"5","key":"10.1124\/dmd.119.087023_bib29","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nrd.2016.268","article-title":"Strategies and challenges for the next generation of antibody-drug conjugates","volume":"16","author":"Beck","year":"2017","journal-title":"Nat Rev Drug Discov"},{"key":"10.1124\/dmd.119.087023_bib2","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/978-1-62703-541-5_11","article-title":"Engineering THIOMABs for site-specific conjugation of thiol-reactive linkers","volume":"1045","author":"Bhakta","year":"2013","journal-title":"Methods Mol Biol"},{"key":"10.1124\/dmd.119.087023_bib3","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/nbt832","article-title":"Development of potent monoclonal antibody auristatin conjugates for cancer therapy","volume":"21","author":"Doronina","year":"2003","journal-title":"Nat Biotechnol"},{"key":"10.1124\/dmd.119.087023_bib4","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1208\/s12248-012-9386-x","article-title":"ADME of antibody-maytansinoid conjugates","volume":"14","author":"Erickson","year":"2012","journal-title":"AAPS J"},{"key":"10.1124\/dmd.119.087023_bib5","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1021\/bc400217g","article-title":"A potent anti-CD70 antibody-drug conjugate combining a dimeric pyrrolobenzodiazepine drug with site-specific conjugation technology","volume":"24","author":"Jeffrey","year":"2013","journal-title":"Bioconjug Chem"},{"key":"10.1124\/dmd.119.087023_bib6","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1021\/acsmedchemlett.6b00421","article-title":"Next-generation antibody-drug conjugates (ADCs) for cancer therapy","volume":"7","author":"Junutula","year":"2016","journal-title":"ACS Med Chem Lett"},{"key":"10.1124\/dmd.119.087023_bib7","doi-asserted-by":"crossref","first-page":"3470","DOI":"10.1007\/s11095-014-1584-z","article-title":"Preclinical pharmacokinetic considerations for the development of antibody drug conjugates","volume":"32","author":"Kamath","year":"2015","journal-title":"Pharm Res"},{"key":"10.1124\/dmd.119.087023_bib8","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1021\/bc300491k","article-title":"Total antibody quantification for MMAE-conjugated antibody-drug conjugates: impact of assay format and reagents","volume":"24","author":"Kozak","year":"2013","journal-title":"Bioconjug Chem"},{"key":"10.1124\/dmd.119.087023_bib9","doi-asserted-by":"crossref","first-page":"9280","DOI":"10.1158\/0008-5472.CAN-08-1776","article-title":"Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate","volume":"68","author":"Lewis Phillips","year":"2008","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.119.087023_bib10","doi-asserted-by":"crossref","first-page":"5139","DOI":"10.1158\/1078-0432.CCR-14-3383","article-title":"Preclinical development of an anti-NaPi2b (SLC34A2) antibody-drug conjugate as a therapeutic for non-small cell lung and ovarian cancers","volume":"21","author":"Lin","year":"2015","journal-title":"Clin Cancer Res"},{"key":"10.1124\/dmd.119.087023_bib11","doi-asserted-by":"crossref","first-page":"6437","DOI":"10.1158\/1078-0432.CCR-11-0762","article-title":"Trastuzumab emtansine: a unique antibody-drug conjugate in development for human epidermal growth factor receptor 2-positive cancer","volume":"17","author":"LoRusso","year":"2011","journal-title":"Clin Cancer Res"},{"key":"10.1124\/dmd.119.087023_bib12","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.1124\/dmd.116.073031","article-title":"Antibody drug conjugates differentiate uptake and DNA alkylation of pyrrolobenzodiazepines in tumors from organs of xenograft mice","volume":"44","author":"Ma","year":"2016","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.119.087023_bib13","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/jps.2600710432","article-title":"General derivation of the equation for time to reach a certain fraction of steady state","volume":"71","author":"Perrier","year":"1982","journal-title":"J Pharm Sci"},{"key":"10.1124\/dmd.119.087023_bib14","doi-asserted-by":"crossref","first-page":"7890","DOI":"10.1021\/jm500552c","article-title":"Site-specific trastuzumab maytansinoid antibody-drug conjugates with improved therapeutic activity through linker and antibody engineering","volume":"57","author":"Pillow","year":"2014","journal-title":"J Med Chem"},{"key":"10.1124\/dmd.119.087023_bib15","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1124\/pr.114.009373","article-title":"Antibody drug conjugates for cancer therapy","volume":"68","author":"Polakis","year":"2016","journal-title":"Pharmacol Rev"},{"key":"10.1124\/dmd.119.087023_bib16","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1038\/leu.2010.141","article-title":"Anti-CD22-MCC-DM1: an antibody-drug conjugate with a stable linker for the treatment of non-Hodgkin\u2019s lymphoma","volume":"24","author":"Polson","year":"2010","journal-title":"Leukemia"},{"issue":"20","key":"10.1124\/dmd.119.087023_bib27","doi-asserted-by":"crossref","first-page":"6417","DOI":"10.1158\/1078-0432.CCR-11-0486","article-title":"Antibody-drug conjugates of calicheamicin derivative: gemtuzumab ozogamicin and inotuzumab ozogamicin","volume":"17","author":"Ricart","year":"2011","journal-title":"Clin Cancer Res"},{"issue":"8","key":"10.1124\/dmd.119.087023_bib32","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1021\/acs.bioconjchem.7b00258","article-title":"Development of Efficient Chemistry to Generate Site-Specific Disulfide-Linked Protein- and Peptide-Payload Conjugates: Application to THIOMAB Antibody-Drug Conjugates","volume":"28","author":"Sadowsky","year":"2017","journal-title":"Bioconjug Chem"},{"key":"10.1124\/dmd.119.087023_bib17","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nbt.2108","article-title":"Conjugation site modulates the in vivo stability and therapeutic activity of antibody-drug conjugates","volume":"30","author":"Shen","year":"2012","journal-title":"Nat Biotechnol"},{"issue":"2 Pt A","key":"10.1124\/dmd.119.087023_bib28","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.molimm.2014.09.014","article-title":"Preclinical and clinical development of inotuzumab-ozogamicin in hematological malignancies","volume":"67","author":"Shor","year":"2015","journal-title":"Mol Immunol"},{"key":"10.1124\/dmd.119.087023_bib18","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1126\/science.1241145","article-title":"Antibody therapeutics in cancer","volume":"341","author":"Sliwkowski","year":"2013","journal-title":"Science"},{"issue":"4","key":"10.1124\/dmd.119.087023_bib31","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1021\/acs.bioconjchem.7b00785","article-title":"Modulating Antibody-Drug Conjugate Payload Metabolism by Conjugation Site and Linker Modification","volume":"29","author":"Su","year":"2018","journal-title":"Bioconjug Chem"},{"key":"10.1124\/dmd.119.087023_bib19","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/clpt.2008.170","article-title":"Monoclonal antibody pharmacokinetics and pharmacodynamics","volume":"84","author":"Wang","year":"2008","journal-title":"Clin Pharmacol Ther"},{"key":"10.1124\/dmd.119.087023_bib30","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s40495-017-0118-x","article-title":"LC\u2013MS Challenges in Characterizing and Quantifying Monoclonal Antibodies (mAb) and Antibody-Drug Conjugates (ADC) in Biological Samples","volume":"4","author":"Wei","year":"2018","journal-title":"Curr Pharmacol Reports,"},{"key":"10.1124\/dmd.119.087023_bib20","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1021\/mp5007757","article-title":"Metabolites of antibody-maytansinoid conjugates: characteristics and in vitro potencies","volume":"12","author":"Widdison","year":"2015","journal-title":"Mol Pharm"},{"key":"10.1124\/dmd.119.087023_bib21","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ab.2011.01.004","article-title":"Characterization of intact antibody-drug conjugates from plasma\/serum in vivo by affinity capture capillary liquid chromatography-mass spectrometry","volume":"412","author":"Xu","year":"2011","journal-title":"Anal Biochem"},{"key":"10.1124\/dmd.119.087023_bib22","doi-asserted-by":"crossref","first-page":"3298","DOI":"10.1158\/1078-0432.CCR-14-2035","article-title":"A novel anti-CD22 anthracycline-based antibody-drug conjugate (ADC) that overcomes resistance to auristatin-based ADCs","volume":"21","author":"Yu","year":"2015","journal-title":"Clin Cancer Res"},{"key":"10.1124\/dmd.119.087023_bib23","doi-asserted-by":"crossref","unstructured":"Zhang D, Hop CE, Patilea-Vrana G, Gampa G, Seneviratne HK, Unadkat JD, Kenny JR, Nagapudi K, Di L, Zhou L, et al. (2019) Drug concentration asymmetry in tissues and plasma for small molecule-related therapeutic modalities. Drug Metab Dispos DOI: 10.1124\/dmd.119.086744 [published ahead of print].","DOI":"10.1124\/dmd.119.086744"},{"key":"10.1124\/dmd.119.087023_bib24","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1021\/acsmedchemlett.6b00233","article-title":"Linker immolation determines cell killing activity of disulfide-linked pyrrolobenzodiazepine antibody-drug conjugates","volume":"7","author":"Zhang","year":"2016","journal-title":"ACS Med Chem Lett"},{"key":"10.1124\/dmd.119.087023_bib25","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1158\/1535-7163.MCT-17-0697","article-title":"Intratumoral payload concentration correlates with the activity of antibody-drug conjugates","volume":"17","author":"Zhang","year":"2018","journal-title":"Mol Cancer Ther"},{"key":"10.1124\/dmd.119.087023_bib26","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1124\/dmd.116.070631","article-title":"Chemical structure and concentration of intratumor catabolites determine efficacy of antibody drug conjugates","volume":"44","author":"Zhang","year":"2016","journal-title":"Drug Metab Dispos"}],"container-title":["Drug Metabolism and Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955624078966?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955624078966?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/dmd.119.087023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T18:57:19Z","timestamp":1739905039000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0090955624078966"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10]]},"references-count":32,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["S0090955624078966"],"URL":"https:\/\/doi.org\/10.1124\/dmd.119.087023","relation":{},"ISSN":["0090-9556"],"issn-type":[{"value":"0090-9556","type":"print"}],"subject":[],"published":{"date-parts":[[2019,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Exposure-Efficacy Analysis of Antibody-Drug Conjugates Delivering an Excessive Level of Payload to Tissues","name":"articletitle","label":"Article Title"},{"value":"Drug Metabolism and Disposition","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/dmd.119.087023","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}