HBV-IN-25 is a novel chemical compound that acts as a potent HBV cccDNA reducer when administered orally. It exhibits significant anti-HBeAg potency and anti-HBV activity, with IC50 values of 0.58 μM and 1.15 μM, respectively. Moreover, HBV-IN-25 demonstrates favorable aqueous solubility (LYSA＞452 μg/mL) and no cellular toxicity, making it a promising candidate for further investigation and development [1].

HBV-IN-25, at concentrations ranging from 8-50 μM over a period of 5 days, exhibits anti-HBeAg potency, demonstrated by an IC50 value of 0.58 μM. Additionally, its anti-HBV activity in primary human hepatocytes (PHH) remains consistent or shows a slight decrease, with an IC50 value of 1.15 μM [1].

HBV-IN-25, administered orally at doses of 5, 20, 100, and 300 mg/kg, exhibits favorable pharmacokinetic (PK) attributes and demonstrates remarkable effectiveness in markedly lowering levels of HBV antigens, DNA, and intrahepatic cccDNA as evidenced in the HBVcircle mouse model. The pharmacokinetic parameters for each dosage showed a proportional increase in both maximum concentration (C max) and area under the curve (AUC), indicating significant drug absorption and sustained presence in the system. Furthermore, dose-dependent effects were observed in terminal body weight changes, spinal cord inflammation, demyelination, and the count of apoptotic cells in spinal cord sections, thereby underscoring the compound’s efficacy and potential therapeutic implications.