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.
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页码：239 / 254
页数：16
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