Structure-based design and biochemical evaluation of sulfanilamide derivatives as hepatitis B virus capsid assembly inhibitors

2012 ◽  
Vol 28 (5) ◽  
pp. 916-925 ◽  
Author(s):  
Min-Hyung Cho ◽  
Jin-Su Song ◽  
Hie-Joon Kim ◽  
Sung-Gyoo Park ◽  
Guhung Jung
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Capsid Assembly ◽  
Virus Capsid ◽  
B Virus ◽  
Biochemical Evaluation

scholarly journals A Kinase Chaperones Hepatitis B Virus Capsid Assembly and Captures Capsid Dynamics in vitro

2011 ◽  
Vol 7 (11) ◽  
pp. e1002388 ◽  
Author(s):  
Chao Chen ◽  
Joseph Che-Yen Wang ◽  
Adam Zlotnick
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Capsid Assembly ◽  
Virus Capsid ◽  
B Virus

Safety, tolerability, and pharmacokinetics of the novel hepatitis B virus capsid assembly modulator GST-HG141 in healthy Chinese subjects: a first-in-human single- and multiple-dose escalation trial

2021 ◽  
Author(s):  
Cuiyun Li ◽  
Min Wu ◽  
Hong Zhang ◽  
Jiajia Mai ◽  
Lizhi Yang ◽  
...  
Keyword(s):  
Steady State ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Maximum Plasma ◽  
Capsid Assembly ◽  
Virus Capsid ◽  
B Virus ◽  
The Mean ◽  
Healthy Chinese ◽  
Chinese Subjects

Background: Hepatitis B virus capsid assembly modulators (HBV CAMs) are promising, clinically validated therapeutic agents for the treatment of chronic hepatitis B (CHB). The safety, tolerability, and pharmacokinetic (PK) profiles of GST-HG141, a novel HBV CAM, were evaluated in healthy Chinese volunteers. Method: This phase Ia study included two parts: a double-blinded, randomized, placebo-controlled single-ascending-dose (SAD) (50, 100, 200, 300, 400, or 500 mg) study comprising a food-effect investigation (300 mg), and a multiple-ascending-dose (MAD) (100 or 200 mg BID) study. Result: GST-HG141 reached the maximum plasma concentration (C max ) at 1.25–3.00 h (median T max ). The exposure exhibited a linear increase, while the mean half-life (t 1/2 ) ranged from 13.096 h to 22.121 h. The exposure of GST-HG141 (300 mg) was higher after food intake by about 2.4-fold. In the MAD study, steady-state was reached at around day 5, and the mean trough steady-state concentrations were 423 and 588 ng/mL for 50 and 100mg cohorts, respectively. The ratios of GST-HG141 accumulation were <1.5. GST-HG141 was well tolerated in healthy Chinese subjects. The rates of adverse events (AEs) in the GST-HG141 cohort did not differ from those of the placebo cohort. Conclusion: GST-HG141 was tolerated in healthy Chinese subjects. The safety and PK profiles of GST-HG141 support the further evaluation of its efficacy in individuals with CHB.

Discovery of New Hepatitis B Virus Capsid Assembly Modulators by an Optimal High-Throughput Cell-Based Assay

2019 ◽  
Vol 5 (5) ◽  
pp. 778-787 ◽  
Author(s):  
Yameng Pei ◽  
Chunting Wang ◽  
Haijing Ben ◽  
Lei Wang ◽  
Yao Ma ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
High Throughput ◽  
Capsid Assembly ◽  
Virus Capsid ◽  
B Virus

Pharmacokinetics, safety and tolerability of single- and multiple-ascending doses of JNJ-64530440, a novel hepatitis B virus capsid assembly modulator, in healthy volunteers

2021 ◽  
pp. 135965352110443
Author(s):  
Thomas N Kakuda ◽  
Jeysen Z Yogaratnam ◽  
Christopher Westland ◽  
Edward J Gane ◽  
Christian Schwabe ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Antiviral Activity ◽  
Healthy Volunteers ◽  
Second Generation ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Capsid Assembly ◽  
Virus Capsid ◽  
B Virus

Background Pharmacokinetics and safety of JNJ-64530440, a hepatitis B virus capsid assembly modulator producing normal empty capsids (CAM-N), in healthy volunteers were evaluated. Methods This Phase I study (NCT03439488) was a double-blind, randomised, placebo-controlled study. Adults ( n = 10/cohort, five Asian/five non-Asian), randomised 4:1, received single-ascending doses of oral JNJ-64530440 (first- and second-generation formulations) or placebo under fasted (50, 150, 300 and 900 mg) or fed (300, 750, 1,000, 2000 and 4000 mg) conditions. Multiple-ascending doses of 750 or 2000 mg once daily and 750 mg twice daily JNJ-64530440 (second-generation formulation) for 7 days were evaluated. Pharmacokinetic parameters were estimated from plasma concentrations. Safety was assessed throughout. Results Less than dose-proportional increases in maximum plasma concentrations (Cmax) and area under the plasma concentration–time curves (AUCs) were observed across the doses. Mean plasma half-lives ranged from 9.3 to 14.5 h. Cmax and AUC were ∼two fold higher under fed versus fasting conditions and slightly higher in Asians versus Caucasians. JNJ-64530440 doses ≥750 mg achieved plasma levels higher than protein-binding adjusted concentrations demonstrating in vitro antiviral activity. No serious adverse events (AEs), treatment discontinuations or dose-limiting toxicities were seen. AE frequency/severity did not increase with dose. Conclusions Single (up to 4000 mg) and multiple doses (up to 2000 mg for 7 days) of JNJ-64530440 were well tolerated in healthy volunteers. Multiple doses ≥750 mg/day achieved plasma concentrations expected to have antiviral activity that may lower hepatitis B surface antigen. No clinically relevant differences in tolerability or pharmacokinetic parameters were seen between Asians versus Caucasians.

scholarly journals A heteroaryldihydropyrimidine activates and can misdirect hepatitis B virus capsid assembly

2005 ◽  
Vol 102 (23) ◽  
pp. 8138-8143 ◽  
Author(s):  
S. J. Stray ◽  
C. R. Bourne ◽  
S. Punna ◽  
W. G. Lewis ◽  
M. G. Finn ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Capsid Assembly ◽  
Virus Capsid ◽  
B Virus

scholarly journals Correction to: Pharmacokinetics, Safety and Tolerability of JNJ-56136379, a Novel Hepatitis B Virus Capsid Assembly Modulator, in Healthy Subjects

2020 ◽  
Vol 37 (4) ◽  
pp. 1703-1703
Author(s):  
Joris Vandenbossche ◽  
Wolfgang Jessner ◽  
Maarten van den Boer ◽  
Jeike Biewenga ◽  
Jan Martin Berke ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Healthy Subjects ◽  
Capsid Assembly ◽  
Virus Capsid ◽  
B Virus
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