使用谷胱甘肽转移酶衍生的2-亚甲基环烯酮对MCF-7(piGST)乳腺肿瘤进行选择性抑制。

Selective inhibition of MCF-7(piGST) breast tumors using glutathione transferase-derived 2-methylene-cycloalkenones.

作者信息

Joseph Erin, Ganem Bruce, Eiseman Julie L, Creighton Donald J

机构信息

Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, MD 21250, USA.

出版信息

J Med Chem. 2005 Oct 20;48(21):6549-52. doi: 10.1021/jm058245f.

DOI:10.1021/jm058245f

PMID:16220971

Abstract

Human glutathione (GSH) transferase (hGSTP1-1) catalyzes the conversion of antitumor 2-crotonyloxymethyl-2-cycloalkenones (COMCs) to highly reactive exocyclic enone alkylating agents. In vitro efficacy studies show that the cytotoxicities of the COMCs directly correlate with the level of expression of GSTP1-1 in MCF-7(piGST) versus MCF-7wt breast tumors, indicating that the exocyclic enones are the actual cytotoxic species. The COMCs are a potentially important new class of prodrugs, which can specifically target multi-drug-resistant tumors overexpressing hGSTP1-1.

摘要

人谷胱甘肽（GSH）转移酶（hGSTP1-1）催化抗肿瘤药物2-巴豆酰氧基甲基-2-环烯酮（COMCs）转化为高反应性的环外烯酮烷基化剂。体外药效学研究表明，COMCs的细胞毒性与MCF-7（piGST）和MCF-7wt乳腺肿瘤中GSTP1-1的表达水平直接相关，这表明环外烯酮是实际的细胞毒性物质。COMCs是一类潜在重要的新型前药，可特异性靶向过表达hGSTP1-1的多药耐药肿瘤。