FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2524928664> ?p ?o ?g. }

• W2524928664 endingPage "1962" @default.
• W2524928664 startingPage "1958" @default.
• W2524928664 abstract "Pyrrolobenzodiazepine (PBD)-dimer is a DNA minor groove alkylator, and its CD22 THIOMAB antibody drug conjugate (ADC) demonstrated, through a disulfide linker, an efficacy in tumor reduction for more than 7 weeks with minimal body weight loss in xenograft mice after a single 0.5–1 mg/kg i.v. dose. The DNA alkylation was investigated here in tumors and healthy organs of mice to understand the sustained efficacy and tolerability. The experimental procedures included the collection of tumors and organ tissues of xenograft mice treated with the ADC followed by DNA isolation/hydrolysis/quantitation and payload recovery from reversible DNA alkylation. PBD-dimer formed a considerable amount of adducts with tissue DNA, representing approximately 98% (at 24 hours), and 99% (at 96 hours) of the total PBD-dimer in tumors, and 78–89% in liver and lung tissues, suggesting highly efficient covalent binding of the released PBD-dimer to tissue DNA. The amount of PBD-DNA adducts in tumor tissues was approximately 24-fold (at 24 hours) and 70-fold (at 96 hours) greater than the corresponding amount of adducts in liver and lung tissues. In addition, the DNA alkylation levels increased 3-fold to 4-fold from 24 to 96 hours in tumors [41/10⁶ base pairs (bp) at 96 hours] but remained at the same level (1/10⁶ bp) in livers and lungs. These results support the typical target-mediated cumulative uptake of ADC into tumors and payload release that offers an explanation for its sustained antitumor efficacy. In addition, the low level of DNA alkylation in normal tissues is consistent with the tolerability observed in mice." @default.
• W2524928664 created "2016-10-07" @default.
• W2524928664 creator A5012042690 @default.
• W2524928664 creator A5022150086 @default.
• W2524928664 creator A5030865863 @default.
• W2524928664 creator A5033020983 @default.
• W2524928664 creator A5052044457 @default.
• W2524928664 creator A5054082820 @default.
• W2524928664 creator A5059244382 @default.
• W2524928664 creator A5066658995 @default.
• W2524928664 creator A5075200671 @default.
• W2524928664 creator A5087222033 @default.
• W2524928664 date "2016-09-28" @default.
• W2524928664 modified "2023-10-03" @default.
• W2524928664 title "Antibody Drug Conjugates Differentiate Uptake and DNA Alkylation of Pyrrolobenzodiazepines in Tumors from Organs of Xenograft Mice" @default.
• W2524928664 cites W1968120820 @default.
• W2524928664 cites W1977998612 @default.
• W2524928664 cites W1995322578 @default.
• W2524928664 cites W2005037511 @default.
• W2524928664 cites W2007342389 @default.
• W2524928664 cites W2020619239 @default.
• W2524928664 cites W2028116753 @default.
• W2524928664 cites W2069254150 @default.
• W2524928664 cites W2073013635 @default.
• W2524928664 cites W2094144162 @default.
• W2524928664 cites W2114180794 @default.
• W2524928664 cites W2120871937 @default.
• W2524928664 cites W2138467280 @default.
• W2524928664 cites W2147696493 @default.
• W2524928664 cites W2167486320 @default.
• W2524928664 cites W2171654274 @default.
• W2524928664 cites W2332250263 @default.
• W2524928664 cites W2341522992 @default.
• W2524928664 cites W2474017875 @default.
• W2524928664 cites W2507318226 @default.
• W2524928664 doi "https://doi.org/10.1124/dmd.116.073031" @default.
• W2524928664 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27683653" @default.
• W2524928664 hasPublicationYear "2016" @default.
• W2524928664 type Work @default.
• W2524928664 sameAs 2524928664 @default.
• W2524928664 citedByCount "22" @default.
• W2524928664 countsByYear W25249286642017 @default.
• W2524928664 countsByYear W25249286642018 @default.
• W2524928664 countsByYear W25249286642019 @default.
• W2524928664 countsByYear W25249286642020 @default.
• W2524928664 countsByYear W25249286642021 @default.
• W2524928664 countsByYear W25249286642022 @default.
• W2524928664 crossrefType "journal-article" @default.
• W2524928664 hasAuthorship W2524928664A5012042690 @default.
• W2524928664 hasAuthorship W2524928664A5022150086 @default.
• W2524928664 hasAuthorship W2524928664A5030865863 @default.
• W2524928664 hasAuthorship W2524928664A5033020983 @default.
• W2524928664 hasAuthorship W2524928664A5052044457 @default.
• W2524928664 hasAuthorship W2524928664A5054082820 @default.
• W2524928664 hasAuthorship W2524928664A5059244382 @default.
• W2524928664 hasAuthorship W2524928664A5066658995 @default.
• W2524928664 hasAuthorship W2524928664A5075200671 @default.
• W2524928664 hasAuthorship W2524928664A5087222033 @default.
• W2524928664 hasBestOaLocation W25249286641 @default.
• W2524928664 hasConcept C108204754 @default.
• W2524928664 hasConcept C111700020 @default.
• W2524928664 hasConcept C134306372 @default.
• W2524928664 hasConcept C150903083 @default.
• W2524928664 hasConcept C153911025 @default.
• W2524928664 hasConcept C159654299 @default.
• W2524928664 hasConcept C161790260 @default.
• W2524928664 hasConcept C164361826 @default.
• W2524928664 hasConcept C178790620 @default.
• W2524928664 hasConcept C185592680 @default.
• W2524928664 hasConcept C197336794 @default.
• W2524928664 hasConcept C203014093 @default.
• W2524928664 hasConcept C207001950 @default.
• W2524928664 hasConcept C2777325958 @default.
• W2524928664 hasConcept C2781247443 @default.
• W2524928664 hasConcept C33923547 @default.
• W2524928664 hasConcept C502942594 @default.
• W2524928664 hasConcept C542903549 @default.
• W2524928664 hasConcept C552990157 @default.
• W2524928664 hasConcept C55493867 @default.
• W2524928664 hasConcept C86803240 @default.
• W2524928664 hasConcept C98274493 @default.
• W2524928664 hasConceptScore W2524928664C108204754 @default.
• W2524928664 hasConceptScore W2524928664C111700020 @default.
• W2524928664 hasConceptScore W2524928664C134306372 @default.
• W2524928664 hasConceptScore W2524928664C150903083 @default.
• W2524928664 hasConceptScore W2524928664C153911025 @default.
• W2524928664 hasConceptScore W2524928664C159654299 @default.
• W2524928664 hasConceptScore W2524928664C161790260 @default.
• W2524928664 hasConceptScore W2524928664C164361826 @default.
• W2524928664 hasConceptScore W2524928664C178790620 @default.
• W2524928664 hasConceptScore W2524928664C185592680 @default.
• W2524928664 hasConceptScore W2524928664C197336794 @default.
• W2524928664 hasConceptScore W2524928664C203014093 @default.
• W2524928664 hasConceptScore W2524928664C207001950 @default.
• W2524928664 hasConceptScore W2524928664C2777325958 @default.
• W2524928664 hasConceptScore W2524928664C2781247443 @default.
• W2524928664 hasConceptScore W2524928664C33923547 @default.
• W2524928664 hasConceptScore W2524928664C502942594 @default.

• next