中国病毒学论坛
10-24 12:04
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近日科学家报道了二氢喹诺酮(DHQ)衍生物的抗HBV活性以及构效关系,其中化合物RG7834是一种具有高度选择性和口服生物活性的乙肝病毒抑制剂,它能抑制病毒抗原和病毒的DNA活性,而且具有新的作用机制。相关研究发表于J. Med. Chem.,题为“Discovery of RG7834: The First-in-Class Selective and Orally Available Small Molecule Hepatitis B Virus Expression Inhibitor with Novel Mechanism of Action”。
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.