A NOVEL ENEDIYNE PRODRUG FOR ANTIBODY-DIRECTED ENZYME PRODRUG THERAPY (ADEPT) USING ESCHERICHIA-COLI-B NITROREDUCTASE

被引:43
作者
HAY, MP
WILSON, WR
DENNY, WA
机构
[1] UNIV AUCKLAND,SCH MED,CANC RES LAB,AUCKLAND,NEW ZEALAND
[2] UNIV AUCKLAND,SCH MED,ONCOL SECT,AUCKLAND,NEW ZEALAND
[3] UNIV AUCKLAND,SCH MED,DEPT PATHOL,AUCKLAND,NEW ZEALAND
关键词
D O I
10.1016/0960-894X(95)00495-F
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The synthesis of a novel enediyne 2, and its cytotoxicity and activation by the nitroreductase enzyme NR2 from Esherichia coli B, are described. In contrast to closely related analogues, 2 exhibits a 90-fold increase in cytoxicity against UV4 cells in the presence of the enzyme and NADH, suggesting its potential as a prodrug for Antibody-Directed Enzyme Prodrug Therapy in conjunction with E. coli nitroreductase.
引用
收藏
页码:2829 / 2834
页数:6
相关论文
共 21 条
[1]   THE BIOACTIVATION OF 5-(AZIRIDIN-1-YL)-2,4-DINITROBENZAMIDE (CB1954) .1. PURIFICATION AND PROPERTIES OF A NITROREDUCTASE ENZYME FROM ESCHERICHIA-COLI - A POTENTIAL ENZYME FOR ANTIBODY-DIRECTED ENZYME PRODRUG THERAPY (ADEPT) [J].
ANLEZARK, GM ;
MELTON, RG ;
SHERWOOD, RF ;
COLES, B ;
FRIEDLOS, F ;
KNOX, RJ .
BIOCHEMICAL PHARMACOLOGY, 1992, 44 (12) :2289-2295
[2]   BIOACTIVATION OF DINITROBENZAMIDE MUSTARDS BY AN ESCHERICHIA-COLI-B NITROREDUCTASE [J].
ANLEZARK, GM ;
MELTON, RG ;
SHERWOOD, RF ;
WILSON, WR ;
DENNY, WA ;
PALMER, BD ;
KNOX, RJ ;
FRIEDLOS, F ;
WILLIAMS, A .
BIOCHEMICAL PHARMACOLOGY, 1995, 50 (05) :609-618
[3]   ANTIBODY-DIRECTED ENZYME PRODRUG THERAPY [J].
BAGSHAWE, KD .
CLINICAL PHARMACOKINETICS, 1994, 27 (05) :368-376
[4]   REACTIVE 1,4-DEHYDROAROMATICS [J].
BERGMAN, RG .
ACCOUNTS OF CHEMICAL RESEARCH, 1973, 6 (01) :25-31
[5]   SITE-SPECIFIC ATOM TRANSFER FROM DNA TO A BOUND LIGAND DEFINES THE GEOMETRY OF A DNA CALICHEAMICIN GAMMA-1I COMPLEX [J].
DEVOSS, JJ ;
TOWNSEND, CA ;
DING, WD ;
MORTON, GO ;
ELLESTAD, GA ;
ZEIN, N ;
TABOR, AB ;
SCHREIBER, SL .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1990, 112 (26) :9669-9670
[6]  
GOLICK J, 1987, J AM CHEM SOC, V109, P3463
[7]   TUMOR TARGETING - ACTIVATION OF PRODRUGS BY ENZYME-MONOCLONAL ANTIBODY CONJUGATES [J].
HUENNEKENS, FM .
TRENDS IN BIOTECHNOLOGY, 1994, 12 (06) :234-239
[8]   THE BIOACTIVATION OF 5-(AZIRIDIN-1-YL)-2,4-DINITROBENZAMIDE (CB1954) .2. A COMPARISON OF AN ESCHERICHIA-COLI NITROREDUCTASE AND WALKER DT DIAPHORASE [J].
KNOX, RJ ;
FRIEDLOS, F ;
SHERWOOD, RF ;
MELTON, RG ;
ANLEZARK, GM .
BIOCHEMICAL PHARMACOLOGY, 1992, 44 (12) :2297-2301
[9]   THE BIOACTIVATION OF CB-1954 AND ITS USE AS A PRODRUG IN ANTIBODY-DIRECTED ENZYME PRODRUG THERAPY (ADEPT) [J].
KNOX, RJ ;
FRIEDLOS, F ;
BOLAND, MP .
CANCER AND METASTASIS REVIEWS, 1993, 12 (02) :195-212
[10]   CALICHEMICINS, A NOVEL FAMILY OF ANTITUMOR ANTIBIOTICS .1. CHEMISTRY AND PARTIAL STRUCTURE OF CALICHEMICIN-GAMMA-1 [J].
LEE, MD ;
DUNNE, TS ;
SIEGEL, MM ;
CHANG, CC ;
MORTON, GO ;
BORDERS, DB .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1987, 109 (11) :3464-3466