L-S,R-buthionine sulfoximine:: historical development and clinical issues

被引：161

作者：

Bailey, HH ^{[1
]}

机构：

[1] Univ Wisconsin, Dept Med, Ctr Comprehens Canc, Madison, WI 53792 USA

来源：

CHEMICO-BIOLOGICAL INTERACTIONS | 1998年 / 112卷

关键词：

L-S; R-buthionine sulfoximine; glutathione; tumor;

D O I：

10.1016/S0009-2797(97)00164-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

L-S,R-buthionine sulfoximine (L-S,R BSO) is a potent specific inhibitor of gamma-glutamylcysteine synthetase, the rate-limiting step in glutathione (GSH) biosynthesis. GSH is an important component of tumor drug resistance based on a strong association and recent transfection studies. Depletion of intracellular GSH by BSO significantly enhances the cytotoxicity of many cytotoxic agents, principally alkylating agents and platinating compounds but also irradiation and anthracyclines. Phase I clinical trials of BSO + melphalan (L-PAM)have been carried out and observed little toxicity with BSO alone and increased myelosuppression with BSO + L-PAM. Consistent and profound ( < 10% of control) GSH depletion was observed in serial determinations of tumor GSH levels in patients receiving continuous infusion (CI) BSO. Evidence of clinical activity has been observed in patients with alkylating or platinating agent-refractory tumors. Phase II evaluation of CI BSO with L-PAM is in progress. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved.

引用

页码：239 / 254

页数：16

共 39 条

[31]

SHRIEVE DC, 1986, CANCER RES, V46, P1684

[32] BUTHIONINE SULFOXIMINE-MEDIATED DEPLETION OF GLUTATHIONE IN INTRACRANIAL HUMAN GLIOMA-DERIVED XENOGRAFTS [J].

SKAPEK, SX ;

COLVIN, OM ;

GRIFFITH, OW ;

GROOTHUIS, DR ;

COLAPINTO, EV ;

LEE, Y ;

HILTON, J ;

ELION, GB ;

BIGNER, DD ;

FRIEDMAN, HS .

BIOCHEMICAL PHARMACOLOGY, 1988, 37 (22) :4313-4317

[33] REDUCTION IN CELLULAR GLUTATHIONE BY BUTHIONINE SULFOXIMINE AND SENSITIZATION OF MURINE TUMOR-CELLS RESISTANT TO L-PHENYLALANINE MUSTARD [J].

SOMFAIRELLE, S ;

SUZUKAKE, K ;

VISTICA, BP ;

VISTICA, DT .

BIOCHEMICAL PHARMACOLOGY, 1984, 33 (03) :485-490

[34] DECHLORINATION OF L-PHENYLALANINE MUSTARD BY SENSITIVE AND RESISTANT TUMOR-CELLS AND ITS RELATIONSHIP TO INTRACELLULAR GLUTATHIONE CONTENT [J].

SUZUKAKE, K ;

VISTICA, BP ;

VISTICA, DT .

BIOCHEMICAL PHARMACOLOGY, 1983, 32 (01) :165-167

[35]

SUZUKAKE K, 1982, BIOCHEM PHARMACOL, V31, P121

[36]

TEW KD, 1994, CANCER RES, V54, P4313

[37]

Vanhoefer U, 1996, CLIN CANCER RES, V2, P1961

[38]

VISTICA DT, 1989, GLUTATHIONE CENTENNI, P300

[39] ROLE OF GLUTATHIONE IN THE EXPORT OF COMPOUNDS FROM CELLS BY THE MULTIDRUG-RESISTANCE-ASSOCIATED PROTEIN [J].

ZAMAN, GJR ;

LANKELMA, J ;

VANTELLINGEN, O ;

BEIJNEN, J ;

DEKKER, H ;

PAULUSMA, C ;

OUDEELFERINK, RPJ ;

BAAS, F ;

BORST, P .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (17) :7690-7694

← 1 2 3 4 →