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Tat介导的反式激活抑制剂鉴定的最新进展:迈向HIV功能性治愈

Recent advances in the identification of Tat-mediated transactivation inhibitors: progressing toward a functional cure of HIV.

作者信息

Tabarrini Oriana, Desantis Jenny, Massari Serena

机构信息

Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo 1, 06123 Perugia, Italy.

出版信息

Future Med Chem. 2016;8(4):421-42. doi: 10.4155/fmc.16.3. Epub 2016 Mar 2.

Abstract

The current anti-HIV combination therapy does not eradicate the virus that persists mainly in quiescent infected CD4(+) T cells as a latent integrated provirus that resumes after therapy interruption. The Tat-mediated transactivation (TMT) is a critical step in the HIV replication cycle that could give the opportunity to reduce the size of latent reservoirs. More than two decades of research led to the identification of various TMT inhibitors. While none of them met the criteria to reach the market, the search for a suitable TMT inhibitor is still actively pursued. Really promising compounds, including one in a Phase III clinical trial, have been recently identified, thus warranting an update.

摘要

目前的抗HIV联合疗法无法根除病毒,该病毒主要以潜伏整合前病毒的形式存在于静止感染的CD4(+) T细胞中,在治疗中断后会重新活跃起来。Tat介导的反式激活(TMT)是HIV复制周期中的关键步骤,这可能为减少潜伏库的规模提供契机。二十多年的研究已鉴定出多种TMT抑制剂。虽然它们都未达到上市标准,但寻找合适的TMT抑制剂的工作仍在积极进行。最近已鉴定出一些非常有前景的化合物,其中一种正在进行III期临床试验,因此有必要进行更新。

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