HBV-IN-25

HBV-IN-25 is a good potency, orally active novel HBV cccDNA reducer. HBV-IN-25 has anti-HBeAg potency and anti-HBV activity with IC50 values of 0.58 μM and 1.15 μM, respectively. HBV-IN-25 has good aqueous solubility (LYSA＞452 μg/mL) and good PK property with no cellular toxicity[1].

Research Areas >> Infection

Signaling Pathways >> Anti-infection >> HBV

IC50: 0.58 μM (anti-HBeAg); 1.15 μM (anti-HBV)[1].

HBV-IN-25 (8-50 μM, 5 days) has anti-HBeAg potency with an IC50 value of 0.58 μM. HBV-IN-25 (8-50 μM, 5 days) has the anti-HBV activity in PHH is maintained or slightly decreased with IC50 value of 1.15 μM[1].

HBV-IN-25 (oral, 5, 20, 100, 300 mg/kg, single) has good PK property, and also shows excellent efficacy in significantly reducing HBV antigens, DNA, and intrahepatic cccDNA levels[1]. Pharmacokinetic Parameters of HBV-IN-25 inHBVcircle mouse model (oral, 5, 20, 100, 300 mg/kg, single)[1]. Dose Terminal body weight % versus day 1 Spinal cord inflammation Foci per 20 cells Spinal cord demyelination Score 0–5 Spinal cord apoptotic cells Count per section PK parameter 5 mg/kg PO 20 mg/kg PO 100 mg/kg PO 300 mg/kg PO Cmax(ng/kg) 828 8157 32200 59900 Tmax(ng/kg) 0.25 0.5 0.5 2.67 AUC0−∞(ng h/mL) 857 11,818 119,960 453,367 t1/2(h) 3.46 3.45 1.82 dose-normalized Cmax[(ng/mL)/(mg/kg)] 166 408 322 200 Dose-normalized AUC0−24h [(ng h/mL)/(mg/kg)] 171 591 1200 1511 Animal Model: HBVcircle mouse model[1] Dosage: 5, 20, 100, 300 mg/kg Administration: oral, 5, 20, 100, 300 mg/kg, single Result:

[1]. Dongdong Chen, et al. Discovery of Novel cccDNA Reducers toward the Cure of Hepatitis B Virus Infection. J Med Chem. 2022 Aug 16.