FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2893386726> ?p ?o ?g. }

• W2893386726 abstract "Among the numerous antibody-drug conjugate (ADC) clinical candidates, one of the most prevalent types utilizes the interchain cysteines in antibodies to conjugate auristatin via a maleimide-containing linker. In this class of ADCs, there are a paucity of systematic studies characterizing how IgG subclass influences the biophysical properties and in vivo pharmacokinetics of the ADC molecules. In the current investigation, we studied cysteine-conjugated ADCs using a model system consisting of human IgG1, IgG2, and IgG4 antibodies with the same variable region. Our findings identified some unforeseen differences among the three ADCs. Drug conjugation profiling by LC-MS revealed that 50% of inter heavy-light chain disulfide bonds are disrupted to conjugate drugs in IgG1 antibody while only 10% in IgG2 antibody and 20% in IgG4 antibody. The solution behavior of the ADCs was interrogated in concentrating experiments and diffusion interaction parameter measurements. We found that drug conjugation affected the solution property of the three antibodies differently, with the IgG2-based ADC having the most increased propensity to aggregate. Rat PK studies using a sensitive LC-MS-based bioanalytical method showed that the IgG1-based ADC has poor peripheral linker-payload stability while the IgG2- and IgG4-based ADCs are stable. The conjugate stability of the IgG2-based ADC was further confirmed in a cynomolgus monkey PK study. Overall, the IgG2-based ADC exhibited the best PK/conjugate stability but also the most deterioration in stability among the three ADCs. Our findings provide important information and present multifactorial considerations for the selection of IgG subclass during ADC drug discovery when employing stochastic cysteine conjugation." @default.
• W2893386726 created "2018-10-05" @default.
• W2893386726 creator A5005959934 @default.
• W2893386726 creator A5006951392 @default.
• W2893386726 creator A5007299647 @default.
• W2893386726 creator A5028185670 @default.
• W2893386726 creator A5030748103 @default.
• W2893386726 creator A5046986458 @default.
• W2893386726 creator A5055398454 @default.
• W2893386726 date "2018-09-25" @default.
• W2893386726 modified "2023-09-26" @default.
• W2893386726 title "The Properties of Cysteine-Conjugated Antibody-Drug Conjugates Are Impacted by the IgG Subclass" @default.
• W2893386726 cites W1555361166 @default.
• W2893386726 cites W1965278354 @default.
• W2893386726 cites W1975553571 @default.
• W2893386726 cites W1976554179 @default.
• W2893386726 cites W1976636554 @default.
• W2893386726 cites W1976973308 @default.
• W2893386726 cites W1992175481 @default.
• W2893386726 cites W1996810499 @default.
• W2893386726 cites W1997021667 @default.
• W2893386726 cites W1998744147 @default.
• W2893386726 cites W2000375213 @default.
• W2893386726 cites W2000621110 @default.
• W2893386726 cites W2004290717 @default.
• W2893386726 cites W2005971097 @default.
• W2893386726 cites W2018478612 @default.
• W2893386726 cites W2023034663 @default.
• W2893386726 cites W2037840717 @default.
• W2893386726 cites W2038319340 @default.
• W2893386726 cites W2042712910 @default.
• W2893386726 cites W2043306817 @default.
• W2893386726 cites W2046476894 @default.
• W2893386726 cites W2047268233 @default.
• W2893386726 cites W2053800409 @default.
• W2893386726 cites W2055546194 @default.
• W2893386726 cites W2063142069 @default.
• W2893386726 cites W2065770280 @default.
• W2893386726 cites W2071163127 @default.
• W2893386726 cites W2073176225 @default.
• W2893386726 cites W2081939392 @default.
• W2893386726 cites W2082419289 @default.
• W2893386726 cites W2083557122 @default.
• W2893386726 cites W2086139797 @default.
• W2893386726 cites W2090057677 @default.
• W2893386726 cites W2091381410 @default.
• W2893386726 cites W2093580676 @default.
• W2893386726 cites W2094423969 @default.
• W2893386726 cites W2108791168 @default.
• W2893386726 cites W2109167399 @default.
• W2893386726 cites W2119870604 @default.
• W2893386726 cites W2126075421 @default.
• W2893386726 cites W2137463204 @default.
• W2893386726 cites W2141301556 @default.
• W2893386726 cites W2167463450 @default.
• W2893386726 cites W2171368669 @default.
• W2893386726 cites W2264135667 @default.
• W2893386726 cites W2277737065 @default.
• W2893386726 cites W2288867196 @default.
• W2893386726 cites W2314837202 @default.
• W2893386726 cites W2332250263 @default.
• W2893386726 cites W2377832514 @default.
• W2893386726 cites W2394619010 @default.
• W2893386726 cites W2409592001 @default.
• W2893386726 cites W2416202632 @default.
• W2893386726 cites W2417088662 @default.
• W2893386726 cites W2561221972 @default.
• W2893386726 cites W2597045666 @default.
• W2893386726 cites W2610971372 @default.
• W2893386726 cites W2619867544 @default.
• W2893386726 cites W2626436697 @default.
• W2893386726 cites W2729256052 @default.
• W2893386726 cites W2763907629 @default.
• W2893386726 cites W2766298702 @default.
• W2893386726 cites W2788615048 @default.
• W2893386726 cites W2791146416 @default.
• W2893386726 cites W39870349 @default.
• W2893386726 doi "https://doi.org/10.1208/s12248-018-0263-0" @default.
• W2893386726 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30255287" @default.
• W2893386726 hasPublicationYear "2018" @default.
• W2893386726 type Work @default.
• W2893386726 sameAs 2893386726 @default.
• W2893386726 citedByCount "10" @default.
• W2893386726 countsByYear W28933867262019 @default.
• W2893386726 countsByYear W28933867262020 @default.
• W2893386726 countsByYear W28933867262021 @default.
• W2893386726 countsByYear W28933867262022 @default.
• W2893386726 countsByYear W28933867262023 @default.
• W2893386726 crossrefType "journal-article" @default.
• W2893386726 hasAuthorship W2893386726A5005959934 @default.
• W2893386726 hasAuthorship W2893386726A5006951392 @default.
• W2893386726 hasAuthorship W2893386726A5007299647 @default.
• W2893386726 hasAuthorship W2893386726A5028185670 @default.
• W2893386726 hasAuthorship W2893386726A5030748103 @default.
• W2893386726 hasAuthorship W2893386726A5046986458 @default.
• W2893386726 hasAuthorship W2893386726A5055398454 @default.
• W2893386726 hasBestOaLocation W28933867261 @default.
• W2893386726 hasConcept C111919701 @default.
• W2893386726 hasConcept C112613896 @default.
• W2893386726 hasConcept C12554922 @default.

• next