Islatravir:艾滋病毒和 HBV 临床开发评估。

IF 4.9 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Samuel W Gillespie, Athreya S Reddy, Dana M Burris, S Hasan Naqvi, Siddappa N Byrareddy, Christian L Lorson, Kamal Singh
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引用次数: 0

摘要

简介伊斯拉曲韦(ISL)是一种核苷类逆转录酶转位抑制剂(NRTTI),可通过多种机制抑制艾滋病病毒 RT。与所有已批准的 NtRTIs 不同,Islatravir 保留了 3'OH 基团。体外和临床数据显示,ISL是一种具有高度耐受性的强效试验药物:介绍了伊斯拉曲韦的历史发展及其抑制 HIV 和 HBV 以及产生耐药性的机制。此外,还讨论了一期和二期临床试验的结果:目前的一线抗逆转录病毒疗法、暴露前和暴露后预防性干预措施在维持低病毒载量或检测不到病毒载量方面非常有效。尽管采取了这些措施,但每年异常高的新感染率要求开发新型抗病毒药物,以抑制耐药艾滋病病毒并提高依从性。曾被视为长效药物的 NRTTI 药物 ISL 已被临床搁置。目前正在进行的减少 ISL 剂量的临床试验结果将决定其未来的临床应用。此外,通过与 ISL 相同的机制抑制艾滋病毒的 MK-8527 可能会取代 ISL。有关 ISL 抑制 HBV 的数据很少,临床前数据显示 ISL 对 HBV 的疗效大大低于目前首选的核苷(t)ide 药物,这表明 ISL 可能不是一种有效的抗 HBV 药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Islatravir: evaluation of clinical development for HIV and HBV.

Introduction: Islatravir (ISL) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) that inhibits HIV RT through multiple mechanisms. Contrary to all approved NtRTIs, islatravir retains a 3'OH group. In vitro and clinical data show that ISL is an ultrapotent investigational drug with high tolerability.

Areas covered: The historical development of islatravir and its mechanisms of HIV and HBV inhibition and resistance are covered. Additionally, the outcomes of Phase I and Phase II clinical trials are discussed.

Expert opinion: Current first-line antiretroviral therapy, preexposure, and postexposure prophylactic interventions are highly effective in maintaining low or undetectable viral load. Despite these measures, an unusually high rate of new infections every year warrants developing novel antivirals that can suppress drug-resistant HIV and improve compliance. ISL, an NRTTI once deemed a long-acting drug, was placed on a clinical hold. The outcome of ongoing clinical trials with a reduced ISL dose will decide its future clinical application. Additionally, MK-8527, which inhibits HIV via same mechanism as that of ISL may supersede ISL. Data on ISL inhibition of HBV are scarce, and preclinical data show dramatically lower ISL efficacy against HBV than currently preferred nucleos(t)ide drugs, indicating that ISL may not be a potent anti-HBV drug.

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来源期刊
CiteScore
10.00
自引率
0.00%
发文量
71
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Investigational Drugs (ISSN 1354-3784 [print], 1744-7658 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles and original papers on drugs in preclinical and early stage clinical development, providing expert opinion on the scope for future development. The Editors welcome: Reviews covering preclinical through to Phase II data on drugs or drug classes for specific indications, and their potential impact on future treatment strategies Drug Evaluations reviewing the clinical and pharmacological data on a particular drug Original Research papers reporting the results of clinical investigations on agents that are in Phase I and II clinical trials The audience consists of scientists, managers and decision-makers in the pharmaceutical industry, and others closely involved in R&D.
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