l-S,R-buthionine sulfoximine: historical development and clinical issues
作者： Howard H Bailey
DOI: 10.1016/S0009-2797(97)00164-6
关键词:
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 an important component tumor drug resistance based on strong association and recent transfection studies. Depletion intracellular by BSO significantly enhances cytotoxicity many cytotoxic agents, principally alkylating agents platinating compounds but also irradiation anthracyclines. Phase I clinical trials + melphalan (L-PAM)have been carried out observed little toxicity with alone increased myelosuppression L-PAM. Consistent profound (< 10% control) depletion was serial determinations levels patients receiving continuous infusion (CI) BSO. Evidence activity has or agent-refractory tumors. II evaluation CI L-PAM progress.
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