JNJ-632 is a hepatitis B virus (HBV) capsid assembly modulator (CAM).
JNJ-632 is a capsid assembly modulator inhibiting hepatitis B virus (HBV). JNJ-632 inhibits HBV DNA HepG2.2.15 and HBV DNA HepG2.117 with EC50s of 0.12 and 0.43 uM, respectively. In the high-content multiparameter cytotoxicity (HepG2), JNJ-632 shows EC20s in the 10-30 uM range (considered weakly cytotoxic)[1].
The single dose PK profile of JNJ-632 is evaluated in C57BL/6 mice following intravenous (iv) and oral (po) administration. JNJ-632 has a moderate plasma clearance of 34 mL/min/kg and a moderate volume of distribution of 1.3 L/kg. The oral bioavailability is 40% following oral administration of 10 mg/kg and 66% following oral administration of 50 mg/kg. JNJ-632 has moderate terminal elimination half-life with t1/2s of 0.42±0.06 h, 1.1±0.67 h, 2.4±2.3 h, and 5.3±0.1 h for 2.5 mg/kg (iv), 10 mg/kg (po), 50 mg/kg (po), and 50 mg/kg (sc).To circumvent the first pass metabolism, JNJ-632 is also dosed subcutaneously at 50 mg/kg in C57BL/6 mice and this results in a concentration in plasma after 24 h of dosing of 102 ng/mL and concentration in liver after 24 h of dosing of 1297 ng/g[1].
References:
[1]. Vandyck K, et al. Synthesis and Evaluation of N-Phenyl-3-sulfamoyl-benzamide Derivatives as Capsid Assembly Modulators Inhibiting Hepatitis B Virus (HBV). J Med Chem. 2018 Jul 26;61(14):6247-6260.