TABLE 14

Bioactivating enzymes and prodrugs used in ADEPT, GDEPT, and VDEPT

Enzyme Prodrug Drug Reference
Nitroreductase CB 1954 5-(Aziridin-1-yl)-4- hydroxyl-amino-2-nitro- benzamide Knox et al., 1992
Cytochrome P450 4-Ipomeanol Unidentified (furan epoxide is speculated) Mohr et al., 2000a
Cytochrome P450 Ifosfamide Isophosphoramide mustard Waxman et al., 1999
Cytochrome P450 Cyclophosphamide Phosphoramide mustard Waxman et al., 1999
Purine-nucleoside phosphorylase Fludarabine 2-Fluoroadenine Huang and Plunkett, 1987
Purine-nucleoside phosphorylase MeP-dR MeP Sorscher et al., 1994
Thymidine kinase Ganciclovir Ganciclovir-triphosphate nucleotide Moolten, 1986
Alkaline phosphatase Etoposide phosphate Etoposide Senter et al., 1988
Alkaline phosphatase Mitomycin C phosphate Mitomycin C Senter et al., 1989
Alkaline phosphatase POMP POM Wallace and Senter, 1991
Alkaline phosphatase N-(4-phosphonooxy)-phenylacetyl)doxorubicin Doxorubicin Vrudhula et al., 1993a
β-Glucuronidase Glucuronidated Nornitrogen mustard Oxazolidinone Papot et al., 2000
β-Glucuronidase Glucuronidated 9-amino-camptothecin 9-Aminocamptothecin Leu et al., 1999
β-Glucuronidase Glucuronide mustard Mustard Lougerstay-Madec et al., 1998
Carboxypeptidase Methotrexate-amino acids Methotrexate Dubowchik and Walker, 1999
Carboxypeptidase CMDA Benzoic acid mustard Blakey et al., 1993
Penicillin amidase DPO Doxorubicin Kerr et al., 1990
Penicillin amidase MelPO Melphalan Kerr et al., 1990
Penicillin amidase NHPAP Palytoxin Bignami et al., 1992
Penicillin amidase N-(phenylacetyl) doxorubicin Doxorubicin Vrudhula et al., 1993a
Penicillin amidase N-(phenylacetyl) melphalan Melphalan Vrudhula et al., 1993a
β-Lactamase LY 266070 DAVLBHYD Jungheim et al., 1992
β-Lactamase C-DOX Doxorubicin Hudyma et al., 1993
β-Lactamase PRODOX Doxorubicin Jungheim et al., 1993
β-Lactamase CM Phenylenediamine mustard Svensson et al., 1992
β-Lactamase CCM Phenylenediamine mustard Vrudhula et al., 1993b
β-Lactamase Cephalosporin-DACCP DACCP Hanessian and Wang, 1993
β-Lactamase PROTAX Taxol Rodrigues et al., 1995a
β-Lactamase Cephalosporin mitomycin C Mitomycin C Vrudhula et al., 1997
β-Lactamase C-Mel Melphalan Kerr et al., 1998
Cytosine deaminase 5-Fluorocytosine 5-Fluorouracil Senter et al., 1991
Methionine γ-lyase Selenomethionine Methylselenol Miki et al., 2001
Methionine γ-lyase Trifluoromethionine CSF2 Coombs and Mottram, 2001

  • MeP, 6-methylpurine; POMP, p-[N,N-bis(2-chloroethyl)amino]phenyl phosphate; POM, p-[N,N-bis(2-chloroethyl)amino]phenol; DAVLBHYD, 4-desacetylvinblastine-3-carboxylic acid hydrazide; DACCP, 4′-carboxyphthalato(1,2-cyclohexanediamine) platinum; CSF2, carbonothionic difluoride.