The HBV core protein plays important roles in HBV lifecycle, with the most prominent one as the essential component of the nucleocapsid. Interrupting the assembly of core protein into nucleocapsid will block the HBV replication. The core protein is conserved across all HBV genotypes and is thus considered as an attractive target for small molecule intervention. This talk will focus on the discovery and development of a novel, Class I Core protein Assembly Modulator (CpAM).<br/><br/>Compared to previous CpAMs, this new series of Class I CpAM showed greatly increased anti-HBV activity due to an unexpected cooperative H-bonding effect with HBV core protein. The photoaffinity study and the co-crystal structure nicely elucidated how the compound binds to the core proteins and exert strong binding affinity. Further optimization addressed CYP3A4 induction issue of the front-runner and eventually led to the discovery of current clinical candidate with desired liver enrichment, optimal mouse PK/PD, and preclinical safety profiles. The phase I clinical safety and efficacy data will be disclosed also.

Discovery and development of a novel, class I Core protein Assembly Modulator (CpAM) for the treatment of chronic HBV infection

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.