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Pharmacokinetics of Jnj-73763989 And Jnj-56136379 (Bersacapavir) In Participants With Moderate Hepatic Impairment
This article is protected by copyright. All rights reserved.PMID:36786053 | DOI:10.1002/jcph.2214
Source: The Journal of Clinical Pharmacology - February 14, 2023 Category: Drugs & Pharmacology Authors: Thomas N Kakuda Atef Halabi Gernot Klein Madhu Sanga Carine Guinard-Azadian Monika Kowalik Katja Nedoschinsky Julius Nangosyah Emmanuel Njumbe Ediage Vera Hillewaert Peter Verboven Ivo Goris Jan Snoeys Martyn Palmer Michael Biermer Source Type: research

Pharmacokinetics, Safety, and Tolerability of the siRNA JNJ ‐73763989 in Healthy Chinese Adult Participants
AbstractJNJ-73763989, composed of the 2 short-interfering RNA triggers JNJ-73763976 and JNJ-73763924, targets all hepatitis B virus messenger RNAs, thereby reducing all viral proteins. In this phase 1, single-site, open-label, parallel-group, randomized study, participants were given 1 subcutaneous injection of JNJ-73763989 (100 or 200  mg) to investigate the pharmacokinetics, safety, and tolerability of JNJ-73763989 in healthy Chinese adult participants. Plasma and urine pharmacokinetic parameters were determined for each trigger up to 48 hours after dosing. Eighteen participants, 9 per dose group, were enrolled. The me...
Source: Clinical Pharmacology in Drug Development - November 23, 2022 Category: Drugs & Pharmacology Authors: Haiyan Li, Xiaoye Niu, Yu Zhang, Danning Zhang, Yanqing Zhang, Liqun Wang, Yongqing Miao, Yanxin Jiang, Jia Ji, Qiaoqiao Chen, Xiaoyun Wu, Emmanuel Njumbe Ediage, Thomas N. Kakuda, Michael Biermer Tags: Original Article Source Type: research

siRNA drug development against hepatitis B virus infection
Volume 18, Issue 6, June 2018, Page 609-617 .
Source: Expert Opinion on Biological Therapy - May 8, 2018 Category: Drugs & Pharmacology Authors: Robert Flisiak Jerzy Jaroszewicz Mariusz Łucejko Source Type: research

Safety, Tolerability, and Pharmacokinetics of ARC ‐520 Injection, an RNA Interference‐Based Therapeutic for the Treatment of Chronic Hepatitis B Virus Infection, in Healthy Volunteers
Abstract ARC‐520 Injection, an RNA interference drug for the treatment of hepatitis B that targets cccDNA‐derived viral mRNA transcripts with high specificity, effectively reduces the production of viral proteins and HBV DNA. In this phase 1 randomized, double‐blind, placebo‐controlled study, 54 healthy volunteers (half male, half female) received a single, intravenous dose of 0.01–4.0 mg/kg ARC‐520 Injection (n = 36) or placebo (n = 18). Assessments included safety, tolerability, pharmacokinetics, and pharmacodynamics (cytokines and complement). Pharmacokinetics of the siRNA and peptide excipient components co...
Source: Clinical Pharmacology in Drug Development - December 11, 2016 Category: Drugs & Pharmacology Authors: Thomas Schluep, Jason Lickliter, James Hamilton, David L. Lewis, Ching ‐Lung Lai, Johnson YN Lau, Stephen A. Locarnini, Robert G. Gish, Bruce D. Given Tags: Original Article Source Type: research

Hepatic Stellate Cells in Liver Fibrosis and siRNA-Based Therapy.
Abstract Hepatic fibrosis is a reversible wound-healing response to either acute or chronic liver injury caused by hepatitis B or C, alcohol, and toxic agents. Hepatic fibrosis is characterized by excessive accumulation and reduced degradation of extracellular matrix (ECM). Excessive accumulation of ECM alters the hepatic architecture leading to liver fibrosis and cirrhosis. Cirrhosis results in failure of common functions of the liver. Hepatic stellate cells (HSC) play a major role in the development of liver fibrosis as HSC are the main source of the excessive production of ECM in an injured liver. RNA interfere...
Source: Pharmacological Reviews - August 17, 2016 Category: Drugs & Pharmacology Authors: Omar R, Yang J, Liu H, Davies NM, Gong Y Tags: Rev Physiol Biochem Pharmacol Source Type: research

Acetylshikonin induces apoptosis of hepatitis B virus X protein-expressing human hepatocellular carcinoma cells via endoplasmic reticulum stress.
Abstract Since it has been known that shikonin derived from a medicinal plant possesses anti-cancer activity, we wonder whether acetylshikonin (ASK), a derivate of shikonin, could be used to treat hepatocellular carcinoma cells expressing hepatitis B virus X protein (HBX), an oncoprotein from hepatitis B virus. When ASK was added to Hep3B cells stably expressing HBX, it induced apoptosis in a dose-dependent manner. ASK induced upregulation and export of Nur77 to the cytoplasm and activation of JNK. Likewise, suppression of Nur77 and JNK inactivation protected the cells from ASK-induced apoptosis, indicating that N...
Source: European Journal of Pharmacology - April 24, 2014 Category: Drugs & Pharmacology Authors: Moon J, Koh SS, Malilas W, Cho IR, Kaewpiboon C, Kaowinn S, Lee K, Jhun BH, Choi YW, Chung YH Tags: Eur J Pharmacol Source Type: research

5'-triphosphate-siRNA activates RIG-I-dependent type I interferon production and enhances inhibition of hepatitis B virus replication in HepG2.2.15 cells.
In conclusion, our findings suggest that 3p-siRNA could act as a powerful bifunctional antiviral molecule with potential for developing a promising therapeutic against chronic HBV infection. PMID: 24099962 [PubMed - as supplied by publisher]
Source: European Journal of Pharmacology - October 4, 2013 Category: Drugs & Pharmacology Authors: Chen X, Qian Y, Yan F, Tu J, Yang X, Xing Y, Chen Z Tags: Eur J Pharmacol Source Type: research