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

被引：123

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

[1]

Bonfanti M, 1999, ANTI-CANCER DRUG DES, V14, P179

[2]

BROGGINI M, 1994, ANTI-CANCER DRUG DES, V9, P373

[3] EFFECTS OF MINOR-GROOVE BINDING-DRUGS ON THE INTERACTION OF TATA BOX-BINDING PROTEIN AND TFIIA WITH DNA [J].

CHIANG, SY ;

WELCH, J ;

RAUSCHER, FJ ;

BEERMAN, TA .

BIOCHEMISTRY, 1994, 33 (23) :7033-7040

[4] Enantioselective total synthesis of ecteinascidin 743 [J].

Corey, EJ ;

Gin, DY ;

Kania, RS .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (38) :9202-9203

[5]

Damia G, 1996, INT J CANCER, V66, P779, DOI 10.1002/(SICI)1097-0215(19960611)66:6<779::AID-IJC12>3.0.CO

[6]

2-Z

[7] Unique pattern of ET-743 activity in different cellular systems with defined deficiencies in DNA-repair pathways [J].

Damia, G ;

Silvestri, S ;

Carrassa, L ;

Filiberti, L ;

Faircloth, GT ;

Liberi, G ;

Foiani, M ;

D'Incalci, M .

INTERNATIONAL JOURNAL OF CANCER, 2001, 92 (04) :583-588

[8] Molecular mechanism of nucleotide excision repair [J].

de Laat, WL ;

Jaspers, NGJ ;

Hoeijmakers, JHJ .

GENES & DEVELOPMENT, 1999, 13 (07) :768-785

[9] Ecteinascidin-743: A marine-derived compound in advanced, pretreated sarcoma patients - Preliminary evidence of activity [J].

Delaloge, S ;

Yovine, A ;

Taamma, A ;

Riofrio, M ;

Brain, E ;

Raymond, E ;

Cottu, P ;

Goldwasser, F ;

Jimeno, J ;

Misset, JL ;

Marty, M ;

Cvitkovic, E .

JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (05) :1248-1255

[10]

DEMETRI GD, 2001, P AM SOC CLIN ONCOL, P1406

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