ddC- and 3TC-bis(SATE) monophosphate prodrugs overcome cellular resistance mechanisms to HIV-1 associated with cytidine kinase deficiency.

B Gröschel, N Himmel, J Cinatl, C Périgaud, G Gosselin, J L Imbach, H W Doerr, J Cinatl
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引用次数: 13

Abstract

A 2',3'-dideoxycytidine (ddC)-resistant T-lymphoid cell line (MOLT-4/8rddC250), in which deoxycytidine kinase (dCK) gene-expression was decreased when compared with parental cells, has been selected. Cytotoxic and antiretroviral activity of ddC and 3TC was significantly lower in MOLT-4/8rddC250-than in parental MOLT-4/8 cells. ddC- and 3TC-bis(SATE)phosphotriesters completely overcame cellular resistance mechanisms and showed comparable both cytotoxic and antiretroviral activity in parental and ddC-resistant cells.

ddC-和3TC-bis(SATE)单磷酸前药克服与胞苷激酶缺乏相关的HIV-1细胞耐药机制。
选择了一个2',3'-二脱氧胞苷(ddC)抗性t淋巴样细胞株(MOLT-4/8rddC250),其中脱氧胞苷激酶(dCK)基因表达与亲本细胞相比降低。在molt -4/ 8rddc250细胞中,ddC和3TC的细胞毒和抗逆转录病毒活性明显低于亲本MOLT-4/8细胞。ddC-和3TC-bis(SATE)磷酸三酯完全克服了细胞耐药机制,并在亲代和ddC耐药细胞中显示出相当的细胞毒性和抗逆转录病毒活性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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