title: Novel inhibitors of carboxypeptidase G2 (CPG2): potential use in antibody-directed enzyme prodrug therapy.
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.
authors: Imperial College of Science, Technology and Medicine, Charing Cross Site, Medical Oncology, St. Dunstan's Road, London W6 8RF, UK.
authors: T H
authors: TH
authors: Khan
authors: E A
authors: EA
authors: Eno-Amooquaye
authors: F
authors: F
authors: Searle
authors: P J
authors: PJ
authors: Browne
authors: H M
authors: HM
authors: Osborn
authors: P J
authors: PJ
authors: Burke
mesh_terms: D000816:Aniline Mustard / Q000031:analogs & derivatives / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D011355:Prodrugs / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D011623:gamma-Glutamyl Hydrolase / Q000037:antagonists & inhibitors* / Q000494:pharmacology
chemical_list: C096843:(4-(N,N-bis(2-chloroethyl)amino)phenoxycarbonyl)glutamic acid; D000906:Antibodies; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011355:Prodrugs; D000816:Aniline Mustard; D011623:gamma-Glutamyl Hydrolase