J Med Chem. 2018 Oct 4. doi: 10.1021/acs.jmedchem.8b01245. [Epub ahead of print]
Discovery of RG7834: The First-in-Class Selective and Orally Available Small Molecule Hepatitis B Virus Expression Inhibitor with Novel Mechanism of Action.
Han X, Zhou C, Jiang M, Wang Y, Wang J, Cheng Z, Wang M, Liu Y, Liang C, Wang J, Wang Z, Weikert R, Lv W, Xie J, Yu X, Zhou X, Luangsay S, Shen HC, Mayweg AV, Javanbakht H, Yang S.
Abstract
Chronic hepatitis B virus (HBV) infection is a serious public health burden and current therapies cannot achieve satisfactory cure rate. There are high unmet medical needs of novel therapeutic agents with differentiated mechanism of action (MOA) from the current standard of care. RG7834, a compound from the dihydroquinolizinone (DHQ) chemical series, is a first-in-class highly selective and orally bioavailable HBV inhibitor which can reduce both viral antigens and viral DNA with a novel mechanism of action. Here we report the discovery of RG7834 from a phenotypic screening and the structure-activity relationship (SAR) of the DHQ chemical series. RG7834 can selectively inhibit HBV but not other DNA or RNA viruses in a virus panel screening. Both in vitro and in vivo profiles of RG7834 are described herein, and the data support further development of this compound as a chronic HBV therapy.
PMID:
30286292
DOI:
10.1021/acs.jmedchem.8b01245
作者: StephenW 时间: 2018-10-7 14:20
J Med Chem。 2018年10月4日doi：10.1021 / acs.jmedchem.8b01245。 [提前打印]
发现RG7834：一流的选择性和口服可用的小分子乙型肝炎病毒表达抑制剂具有新的作用机制。
Han X，Zhou C，Jiang M，Wang Y，Wang J，Cheng Z，Wang M，Liu Y，Liang C，Wang J，Wang Z，Weikert R，Lv W，Xie J，Yu X，Zhou X，Luangsay S ，Shen HC，Mayweg AV，Javanbakht H，Yang S.
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