Minor groove binder antibody conjugates employing a water soluble β-glucuronide linker

The minor groove binder β-glucuronide drug-linker 3 was constructed from amino CBI 1 and determined to be a substrate for Escherichia coli β-glucuronidase (EC 3.2.1.31), resulting in facile drug release. Compound 3 was conjugated to mAbs cAC10 (anti-CD30) and h1F6 (anti-CD70) to give antibody-drug c...

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 17; no. 8; pp. 2278 - 2280
Main Authors:	Jeffrey, Scott C., Nguyen, Minh T., Moser, Ruth F., Meyer, Damon L., Miyamoto, Jamie B., Senter, Peter D.
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 15-04-2007 Elsevier
Subjects:	Aggregation Anti-CD30 Anti-CD70 Antibodies, Monoclonal - therapeutic use Antibody Antigens, Neoplasm - immunology Antineoplastic Agents, Alkylating - chemical synthesis Antineoplastic Agents, Alkylating - pharmacokinetics Biological and medical sciences cAC10 Cancer Cell Line, Tumor Cell Survival - drug effects Conjugate Cross-Linking Reagents Delivery Drug Drug Delivery Systems - methods Drug-linker Escherichia coli Glucuronates - chemistry Glucuronidase - metabolism h1F6 Humans Immunoconjugates - chemistry Immunoconjugates - metabolism Immunoconjugates - therapeutic use Inhibitory Concentration 50 Linker Medical sciences Minor groove binder Miscellaneous Monoclonal Pharmacology. Drug treatments Prodrugs - chemical synthesis Prodrugs - metabolism Prodrugs - pharmacokinetics Release Solubility Targeted β-Glucuronidase β-Glucuronide Drug β-Glucuronidase Conjugate Antibody Drug-linker h1F6 Linker Aggregation Minor groove binder Targeted Anti-CD30 cAC10 Delivery Monoclonal β-Glucuronide Release Anti-CD70 Cancer Spacer arm hlF6 Escherichia coli Cytotoxicity Monoclonal antibody Organic carbamate Glucuroconjugate Lymphoproliferative syndrome Bacteria Chemical synthesis Tumor cell Enterobacteriaceae Minor groove Enzyme Hodgkin disease Malignant hemopathy In vitro Lymphoma Biological activity Substrate Water soluble compound Cell line Glycosidases Uronic acid Hydrolases Conjugated compound O-Glycosidases
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