Expanded utility of the β-glucuronide linker: ADCs that deliver phenolic cytotoxic agents

Scott C. Jeffrey, Jef De Brabander, Jamie Miyamoto, Peter D. Senter

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)277-280
Number of pages4
JournalACS Medicinal Chemistry Letters
Volume1
Issue number6
DOIs
StatePublished - Sep 9 2010

Fingerprint

Glucuronides
Cytotoxins
Antibodies
Pharmaceutical Preparations
Phenol
Diamines
Glucuronidase
Amines
Cell Line
Cells

Keywords

  • β-Glucuronide linker
  • antibody-drug conjugates
  • CD30-positive L540cy cell line
  • CD70-positive Caki-1 cell line
  • N,N′-dimethylethylene diamine
  • phenolic cytotoxic agents

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

Cite this

Expanded utility of the β-glucuronide linker : ADCs that deliver phenolic cytotoxic agents. / Jeffrey, Scott C.; De Brabander, Jef; Miyamoto, Jamie; Senter, Peter D.

In: ACS Medicinal Chemistry Letters, Vol. 1, No. 6, 09.09.2010, p. 277-280.

Research output: Contribution to journalArticle

Jeffrey, Scott C. ; De Brabander, Jef ; Miyamoto, Jamie ; Senter, Peter D. / Expanded utility of the β-glucuronide linker : ADCs that deliver phenolic cytotoxic agents. In: ACS Medicinal Chemistry Letters. 2010 ; Vol. 1, No. 6. pp. 277-280.
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