PROTACHBeAg degrader-1 is a PROTAC-based targeted degrader of HBeAg. It effectively recruits the VHL E3 ligase, yet its ability to degrade the hepatitis B virus protein (HBeAg) does not depend on VHL recruitment. This compound decreases levels of both secreted and intracellular HBeAg and is suitable for research involving the hepatitis B virus (HBV).

PROTAC HBeAg degrader-1 (Compound LH-3) at concentrations ranging from 0.1 to 100 μM over 24 hours, effectively diminishes both secreted and intracellular HBeAg levels in HEK293T HiBiT-HBeAg-S cells in a concentration-dependent manner. At 10 μM for 24 hours, it demonstrates VHL-dependent reduction of HBeAg in HEK293T HiBiT-HBeAg-S cells, without recruiting VHL. Additionally, at 10 μM over a span of 6 days, it causes a significant reduction in HBcAg within HepAD38 cells. Furthermore, at 10 μM for 24 hours, PROTAC HBeAg degrader-1 successfully decreases wild-type HBeAg caused by the T109I HBV mutation in Huh7 cells.