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J Med Chem. 1999 Mar 25;42(6):951-6.

Novel inhibitors of carboxypeptidase G2 (CPG2): potential use in antibody-directed enzyme prodrug therapy.

Author information

1
Imperial College of Science, Technology and Medicine, Charing Cross Site, Medical Oncology, St. Dunstan's Road, London W6 8RF, UK.

Abstract

The design and synthesis of potent thiocarbamate inhibitors for carboxypeptidase G2 are described. The best thiocarbamate inhibitor N-(p-methoxybenzenethiocarbonyl)amino-L-glutamic acid 6d, chosen for preliminary investigations of in vitro antibody-directed enzyme prodrug therapy (ADEPT), abrogated the cytotoxicity of a combination of A5B7-carboxypeptidase G2 conjugate and prodrug PGP (N-p-{N,N-bis (2-chloroethyl)amino}phenoxycarbonyl-L-glutamate) toward LS174T cells. This is the first report of a small-molecule enzyme inhibitor proposed for use in conjunction with the ADEPT approach.

PMID:
10090777
DOI:
10.1021/jm990004i
[Indexed for MEDLINE]

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