2'-氟-6'-亚甲基碳环腺苷及其氨基磷酸酯前体药物:一种新的

StephenW

Med Res Rev. 2018 Feb 6. doi: 10.1002 / med.21490. [Epub ahead of print]
2'-Fluoro-6'-methylene carbocyclic adenosine and its phosphoramidate prodrug: A novel anti-HBV agent, active against drug-resistant HBV mutants.
Singh US1, Mulamoottil VA1, Chu CK1.
Author information

1
    Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA, USA.

Abstract

Currently, clinically approved nucleos (t) ide analogs (NAs) are very efficient in reducing the load of hepatitis B virus (HBV) with minimum side effects. Chronic hepatitis B (CHB) is one of the major causes of morbidity and mortality worldwide. However, the long-term administration of antiviral drugs promotes HBV for potential drug resistance. Herein, 2'-fluoro-6'-methylene carbocyclic adenosine (FMCA) and its phosphoramidate (FMCAP) have been discovered, which may be utilized in combination with therapies for curing drug-resistant chronic hepatitis B. In preclinical studies, these carbocyclic NAs demonstrated potential anti-HBV activity against adefovir, as well as lamivudine (LMV / LAM) drug-resistant mutants. In vitro, these peptides have demonstrated significant activity against LMV / ent Preliminary studies of FMCA / FMCAP in chimeric mice and female Non-obese diabetic / severe combined immunodeficiency (NOD / SCID) mouse models having the LMV / ETV triple mutant shown a high rate of reduction of HBV DNA levels compared to ETV. In this review, we have summarized preclinical studies of FMCA and its phosphoramidate prodrug (FMCAP).
KEYWORDS:

anti-HBV agents; carbocyclic nucleosides; chronic hepatitis B; drug-resistant mutants; nucleos (t) ide analogs

PMID:
    29406612
DOI:
    10.1002 / med.21490

StephenW

Med Res Rev.2018 Feb 6 doi：10.1002 / med.21490。 [电子版提前打印]
2'-氟-6'-亚甲基碳环腺苷及其氨基磷酸酯前体药物：一种新的抗HBV药物，对抗药物性HBV突变体具有活性。
Singh US1，Mulamoottil VA1，Chu CK1。
作者信息

1
美国佐治亚大学制药与生物医学系，美国乔治亚州雅典。

抽象

目前，临床批准的核苷（酸）类似物（NAs）在减少乙肝病毒（HBV）负荷方面非常有效，副作用最小。慢性乙型肝炎（CHB）是世界范围内发病率和死亡率的主要原因之一。然而，抗病毒药物的长期使用会促进HBV的潜在耐药性。在此，已经发现了2'-氟-6'-亚甲基碳环腺苷（FMCA）及其氨基磷酸酯（FMCAP），其可与用于治疗耐药性慢性乙型肝炎的疗法组合使用。在临床前研究中，这些碳环NAs显示出对阿德福韦以及拉米夫定（LMV / LAM）耐药突变体的潜在抗HBV活性。在体外，这些肽已经显示出针对LMV / ent的显着活性嵌合小鼠和具有LMV / ETV三重突变体的雌性非肥胖糖尿病/严重联合免疫缺陷（NOD / SCID）小鼠模型中FMCA / FMCAP的初步研究显示出高的比率与ETV相比，HBV DNA水平降低。在这篇综述中，我们总结了FMCA及其氨基磷酸酯前体药物（FMCAP）的临床前研究。
关键词：

抗HBV药物;碳环核苷;慢性乙型肝炎;耐药突变体;核苷（酸）类似物

结论：
29406612
DOI：
10.1002 / med.21490

jdcy

顶！

Hepbest

发现了2'-氟-6'-亚甲基碳环腺苷（FMCA）及其氨基磷酸酯（FMCAP），其可与用于治疗耐药性慢性乙型肝炎的疗法组合使用。在临床前研究中，这些碳环NAs显示出对阿德福韦以及拉米夫定（LMV / LAM）耐药突变体的潜在抗HBV活性。
——以后可以像HIV那样，组合用药，提高药效，进一步降低副作用