Design, Synthesis, and in vitro Evaluation of Multivalent Drug Linkers for High‐Drug‐Load Antibody–Drug Conjugates

A series of novel multivalent drug linkers (MDLs) containing cytotoxic agents were synthesized and conjugated to antibodies to yield highly potent antibody–drug conjugates (ADCs) with drug/antibody ratios (DARs) higher than those typically reported in the literature (10 vs. ≈4). These MDLs contain t...

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Veröffentlicht in:	ChemMedChem 2018-04, Vol.13 (8), p.790-794
Hauptverfasser:	Chen, Bo, Gianolio, Diego A., Stefano, James E., Manning, Charlene M., Gregory, Richard C., Busch, Michelle M., Brondyk, William H., Miller, Robert J., Dhal, Pradeep K.
Format:	Artikel
Sprache:	eng
Schlagworte:	Agglomeration Antibodies antibody–drug conjugates Antineoplastic Agents, Immunological - chemistry Antineoplastic Agents, Immunological - pharmacology Biocompatibility Cell Line, Tumor Chain branching Conjugates Cytotoxic agents Cytotoxicity Cytotoxins Drug Design Drug development Humans Hydrophobic and Hydrophilic Interactions Hydrophobicity Immunoconjugates - chemistry Immunoconjugates - pharmacology Immunotherapy Monoclonal antibodies multivalent drug linkers Neoplasms - drug therapy Polyethylene glycol Polyethylene Glycols - chemistry Polyethylene Glycols - pharmacology Protein Aggregates Solubility Toxicity trastuzumab Trastuzumab - chemistry Trastuzumab - pharmacology
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