Abstract
The β-glucuronide linker has been used for antibody-drug conjugates (ADCs) to deliver amine-containing cytotoxic agents. The linker is stable in circulation, hydrophilic and provides ADCs that are highly active in vitro and in vivo. To extend the utility of the β-glucuronide linker toward phenol-containing drugs, an N,N′-dimethylethylene diamine self-immolative spacer was incorporated with the linker for release of the potent cytotoxic phenol psymberin A. Exposure of the drug-linker to β-glucuronidase resulted in facile drug release. The corresponding ADCs were active and immunologically selective against CD30-positive L540cy and CD70-positive Caki-1 cell lines.
Original language | English (US) |
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Pages (from-to) | 277-280 |
Number of pages | 4 |
Journal | ACS Medicinal Chemistry Letters |
Volume | 1 |
Issue number | 6 |
DOIs | |
State | Published - Sep 9 2010 |
Keywords
- CD30-positive L540cy cell line
- CD70-positive Caki-1 cell line
- N,N′-dimethylethylene diamine
- antibody-drug conjugates
- phenolic cytotoxic agents
- β-Glucuronide linker
ASJC Scopus subject areas
- Biochemistry
- Drug Discovery
- Organic Chemistry