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下一代HIV-1非核苷类逆转录酶抑制剂

Next-generation HIV-1 non-nucleoside reverse transcriptase inhibitors.

作者信息

Boone Lawrence R

机构信息

GlaxoSmithKline, Discovery Virology, Research Triangle Park, NC 27709, USA.

出版信息

Curr Opin Investig Drugs. 2006 Feb;7(2):128-35.

PMID:16499282
Abstract

This review discusses the desired attributes of a next-generation HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) and highlights the properties of compounds currently or recently in clinical development. TMC-125 is currently in phase III clinical trials and on track to become the first NNRTI suitable for use in NNRTI-experienced patients. TMC-278 is structurally related to TMC-125, but is more potent in vitro and has pharmacokinetics suitable for once-daily administration. It is currently undergoing phase II clinical trials. BILR-355 BS, a dipyridodiazepinone compound, is in early phase II clinical trials. It requires ritonavir as a booster and has reduced inhibitory activity against several key NNRTI-resistant HIV-1 strains. Development of the NNRTIs capravirine and GW-695634 has been discontinued because of lack of efficacy and safety issues, respectively.

摘要

本综述讨论了下一代HIV-1非核苷类逆转录酶抑制剂（NNRTI）所需具备的特性，并着重介绍了目前或近期处于临床开发阶段的化合物的性质。TMC-125目前正处于III期临床试验阶段，有望成为首个适用于有NNRTI治疗史患者的NNRTI。TMC-278在结构上与TMC-125相关，但体外活性更强，且药代动力学特性适合每日一次给药。它目前正在进行II期临床试验。二吡啶并二氮杂䓬酮化合物BILR-355 BS正处于II期临床试验早期阶段。它需要利托那韦作为增效剂，且对几种关键的耐NNRTI HIV-1毒株的抑制活性降低。由于缺乏疗效和安全性问题，NNRTIs类药物卡普瑞韦和GW-695634已停止开发。

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