HIV-1 entry inhibitors: an overview.
HIV-1 entry inhibitors: an overview.
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HIV-1进入抑制剂：概述。
DOI：
10.1097/coh.0b013e328322402e
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发表时间：
2009-03
影响因子：
4.1
通讯作者：
Kuritzkes DR
中科院分区：
文献类型：
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作者：
Kuritzkes DR
本文综述了HIV-1进入抑制剂，重点是趋化因子受体拮抗剂。HIV-1进入靶细胞是一个有序的多步骤过程，包括附着、共受体结合和融合。每个步骤的抑制剂已经被鉴定，并在临床试验中显示具有抗病毒活性。单克隆抗体和小分子附着抑制剂的1-2期试验已经证明了在HIV-1感染受试者中的活性，但没有进展到后期临床试验。附着后抑制剂ibalizumab在1期和2期试验中显示出活性;预计将进行进一步的研究。CCR 5拮抗剂马拉韦罗（现已批准用于临床）和vicriviroc（在3期试验中）在有治疗经验的受试者的对照试验中显示出显著的益处;其他CCR 5拮抗剂处于临床开发的各个阶段。事实证明，靶向CXCR 4更具挑战性。虽然在两种化合物的1-2期试验中已经证明了概念验证，但都不适合长期给药。在开发长效或口服生物可利用的融合抑制剂方面几乎没有进展。ACCR 5拮抗剂和融合抑制剂被批准用作HIV-1进入抑制剂。目前正在开发针对HIV-1进入其他步骤的药物。
This review provides an overview of HIV-1 entry inhibitors, with a focus on chemokine receptor antagonists. Entry of HIV-1 into target cells is an ordered multi-step process involving attachment, co-receptor binding and fusion. Inhibitors of each step have been identified and shown to have antiviral activity in clinical trials. Phase 1-2 trials of monoclonal antibodies and small-molecule attachment inhibitors have demonstrated activity in HIV-1-infected subjects, but none has progressed to later phase clinical trials. The post-attachment inhibitor ibalizumab has shown activity in phase 1 and 2 trials; further studies are anticipated. The CCR5 antagonists maraviroc (now been approved for clinical use) and vicriviroc (in phase 3 trials) have shown significant benefit in controlled trials in treatment-experienced subjects; additional CCR5 antagonists are in various stages of clinical development. Targeting CXCR4 has proven to be more challenging. Although proof of concept has been demonstrated in phase 1-2 trials of two compounds, neither proved suitable for chronic administration. Little progress has been reported in developing longer acting or orally bioavailable fusion inhibitors. ACCR5 antagonist and a fusion inhibitor are approved for use as HIV-1 entry inhibitors. Development of drugs targeting other steps in HIV-1 entry is ongoing.