Ecteinascidin 743: a novel anticancer drug with a unique mechanism of action

被引：121

作者：

Aune, GJ ^{[1
]}

Furuta, T ^{[1
]}

Pommier, Y ^{[1
]}

机构：

[1] NCI, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA

来源：

ANTI-CANCER DRUGS | 2002年 / 13卷 / 06期

关键词：

cancer chemotherapy; DNA alkylation; DNA binding; DNA repair; minor groove binder; transcription;

D O I：

10.1097/00001813-200207000-00001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Ecteinascidin 743 (Et743) is an interesting compound in phase II/III clinical trials. Its chemistry is complex, its mechanism of action is original and it is active in human cancers, such as sarcomas refractory to conventional chemotherapy. The present review describes the discovery of the drug, its specific interactions with DNA and its reversible alkylation mechanism with guanine N-2 in the DNA minor groove. Et743 is a selective transcription inhibitor, which has the unique characteristic of poisoning transcription-coupled nucleotide excision repair. Understanding the molecular pharmacology of Et743 should help in deciding which patients should receive Et743 treatments and which agents should be most useful in association. [(C) 2002 Lippincott Williams Wilkins].

引用

页码：545 / 555

页数：11

共 57 条

[31] DISPLAY AND ANALYSIS OF PATTERNS OF DIFFERENTIAL ACTIVITY OF DRUGS AGAINST HUMAN-TUMOR CELL-LINES - DEVELOPMENT OF MEAN GRAPH AND COMPARE ALGORITHM [J].

PAULL, KD ;

SHOEMAKER, RH ;

HODES, L ;

MONKS, A ;

SCUDIERO, DA ;

RUBINSTEIN, L ;

PLOWMAN, J ;

BOYD, MR .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1989, 81 (14) :1088-1092

[32]

PETRUSEK RL, 1982, J BIOL CHEM, V257, P6207

[33] PYRROLO[1,4]BENZODIAZEPINE ANTIBIOTICS - PROPOSED STRUCTURES AND CHARACTERISTICS OF THE INVITRO DEOXYRIBONUCLEIC-ACID ADDUCTS OF ANTHRAMYCIN, TOMAYMYCIN, SIBIROMYCIN, AND NEOTHRAMYCIN-A AND NEOTHRAMYCIN-B [J].

PETRUSEK, RL ;

ANDERSON, GL ;

GARNER, TF ;

FANNIN, QL ;

KAPLAN, DJ ;

ZIMMER, SG ;

HURLEY, LH .

BIOCHEMISTRY, 1981, 20 (05) :1111-1119

[34] Benzo[a]pyrene diol epoxide adducts in DNA are potent suppressors of a normal topoisomerase I cleavage site and powerful inducers of other topoisomerase I cleavages [J].

Pommier, Y ;

Kohlhagen, G ;

Pourquier, P ;

Sayer, JM ;

Kroth, H ;

Jerina, DM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (05) :2040-2045

[35] DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the Caribbean tunicate Ecteinascidin turbinata [J].

Pommier, Y ;

Kohlhagen, G ;

Bailly, C ;

Waring, M ;

Mazumder, A ;

Kohn, KW .

BIOCHEMISTRY, 1996, 35 (41) :13303-13309

[36]

Rinehart KL, 2000, MED RES REV, V20, P1

[37]

Ryan DP, 2001, CLIN CANCER RES, V7, P231

[38] Ecteinascidins: Putative biosynthetic precursors and absolute stereochemistry [J].

Sakai, R ;

JaresErijman, EA ;

Manzanares, I ;

Elipe, MVS ;

Rinehart, KL .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (38) :9017-9023

[39] ADDITIONAL ANTITUMOR ECTEINASCIDINS FROM A CARIBBEAN TUNICATE - CRYSTAL-STRUCTURES AND ACTIVITIES INVIVO [J].

SAKAI, R ;

RINEHART, KL ;

GUAN, Y ;

WANG, AHJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (23) :11456-11460

[40] Molecular basis for the DNA sequence selectivity of ecteinascidin 736 and 743: Evidence for the dominant role of direct readout via hydrogen bonding [J].

Seaman, FC ;

Hurley, LH .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (50) :13028-13041

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