张兴权. 抗HIV药物的最新研究进展J. 药学学报, 2015,50(5): 509-515.
引用本文: 张兴权. 抗HIV药物的最新研究进展J. 药学学报, 2015,50(5): 509-515.
ZHANG Xing-quan. The newest developments of the study on anti-HIV drugsJ. Acta Pharmaceutica Sinica, 2015,50(5): 509-515.
Citation: ZHANG Xing-quan. The newest developments of the study on anti-HIV drugsJ. Acta Pharmaceutica Sinica, 2015,50(5): 509-515.

抗HIV药物的最新研究进展

The newest developments of the study on anti-HIV drugs

  • 摘要: 目前多种抗逆转录病毒准新药正在2、3期临床评价中。新的核苷逆转录酶抑制剂tenofoviralafenamide- fumarate (TAF) 比替诺福韦 (tenofovir, TDF) 抗病毒活性强且毒性较低; 非核苷逆转录酶抑制剂doravirine对该酶耐受病毒株有效, 而新的整合酶抑制剂GSK744具有长效的特点。此外, 几个具有新的作用机制的化合物也受到关注, 如BMS-663 068小分子化合物是CD4结合的抑制剂, 而cenicriviroc是新颖的CCR5/CCR2受体拮抗剂, 具有抗HIV和抗炎的双重作用。几类针对潜伏病毒感染的药物也正在研发中, 其中组蛋白去乙酰化酶抑制剂发展较快, 其余大多处于体外筛选阶段, 如蛋白激酶C激活剂、DNA甲基转移酶抑制剂、阳性转录延长因子激活剂和组蛋白甲基转移酶抑制剂等。本文对有望近期进入临床使用的新药和可能逆转HIV潜伏感染的化合物进行重点介绍。

     

    Abstract: Besides 36 (28 single-tablets and 8 fixed-dose combinations) used antiretroviral drugs clinically, there are a number of investigational antiretroviral agents currently in phase 2-3 clinical trial. Tenofoviralafenamidefumarate (TAF) is a novel nucleoside analogue reverse transcriptase inhibitor that is potent and less toxicity than tenofovir (TDF). Doravirine is a non-nucleoside analogue reverse transcriptase inhibitor that demonstrates activity against NNRTI-resistant viral strains. GSK744 is an integrase inhibitor with a long acting preparation. In addition, several drugs with new mechanisms are also noted, for example, BMS-663 068 is a small molecule CD4 attachment inhibitors and cenicriviroc is a novel CCR5/CCR2 antagonist with antiretroviral activity and anti-inflammatory effects. Several drug classes that target known pathways in HIV latency have being developed, and leading the list are histone deacetylase inhibitors. Other agents include protein kinase C activators, positive transcription elongation factor activators, DNA methyl-transferase inhibitors and histone methyl-transferase inhibitors and so on. This review is focused on the above-mentioned drug candidates that may be used in clinical in next couple of years and those compounds that can reverse latent HIV infections.

     

/

返回文章
返回