Resistance to lamivudine therapy: is there more than meets the eye?

Dusheiko, Geoffrey; Bertoletti, Antonio

doi:10.1136/gut.2004.047548

Cited by 6 publications

(5 citation statements)

References 29 publications

(8 reference statements)

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“…Although complete suppression of viral replication, as determined by negative serum HBV DNA, may be achieved in most patients, clearance of hepatitis B virus e antigen (HBeAg) with antibody (anti‐HBe) seroconversion was seen only in a minority of patients 1, 3, 5 . The mechanisms of successful lamivudine therapy thus remain to be elucidated 2, 11 …”

Section: Introductionmentioning

confidence: 99%

Poor response to 18‐month lamivudine monotherapy in chronic hepatitis B patients with IgM anti‐HBc and acute exacerbation

Chen

Lin

et al. 2005

Aliment Pharmacol Ther

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Section: Introductionmentioning

confidence: 99%

Poor response to 18‐month lamivudine monotherapy in chronic hepatitis B patients with IgM anti‐HBc and acute exacerbation

Chen

Lin

et al. 2005

Aliment Pharmacol Ther

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“…The nucleoside analogs in treatment of anti-HBV play a role of Troy horse in synthesis of HBV DNA and suppressed replication of HBV, but they are not effective to eliminate virus completely from patients [4,5,6]. Meanwhile, therapies of HBV with nucleoside analogs in the long term cause side effects and resistance [7,8,9]. Therefore, it is still a tremendous challenge to develop new anti-HBV agents for further improvement of anti-HBV therapy.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Bioactive Screen In Vitro of Cyclohexyl (E)-4-(Hydroxyimino)-4-Phenylbutanoates and Their Ethers for Anti-Hepatitis B Virus Agents

et al. 2019

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A series of oxime Cyclohexyl (E)-4-(hydroxyimino)-4-phenylbutanoates and their ethers were designed, synthesized, and evaluated for anti-hepatitis B virus (HBV) activities with HepG 2.2.15 cell line in vitro. Most of these compounds possessed anti-HBV activities, and among them, compound 4B-2 showed significant inhibiting effects on the secretion of HBsAg (IC50 = 63.85 ± 6.26 μM, SI = 13.41) and HBeAg (IC50 = 49.39 ± 4.17 μM, SI = 17.34) comparing to lamivudine (3TC) in HBsAg (IC50 = 234.2 ± 17.17 μM, SI = 2.2) and HBeAg (IC50 = 249.9 ± 21.51 μM, SI = 2.07). Docking study of these compounds binding to a protein residue (PDB ID: 3OX8) from HLA-A2 that with the immunodominant HBcAg18–27 epitope (HLA-A2.1- restricted CTL epitope) active site was carried out by using molecular operation environment (MOE) software. Docking results showed that behaviors of these compounds binding to the active site in HLA-A protein residue partly coincided with their behaviors in vitro anti-HBV active screening.

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“…The nucleoside analogs used in treatment of anti-HBV play the role of Trojan horse in the synthesis of HBV DNA and suppress replication of HBV [ 3 , 4 , 5 , 6 , 7 ], but they are not effective in eliminating the virus from patients. Meanwhile, HBV therapies with nucleoside analogs in the long term cause serious side effects and resistance [ 8 , 9 , 10 , 11 , 12 ]. For the improvement of HBV therapies, the structural modification of nucleoside analogs has focused and developed many derivatives [ 13 , 14 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Discovery of Oxime Ethers as Hepatitis B Virus (HBV) Inhibitors by Docking, Screening and In Vitro Investigation

et al. 2018

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A series of oxime ethers with C6-C4 fragment was designed and virtually bioactively screened by docking with a target, then provided by a Friedel–Crafts reaction, esterification (or amidation), and oximation from p-substituted phenyl derivatives (Methylbenzene, Methoxybenzene, Chlorobenzene). Anti-hepatitis B virus (HBV) activities of all synthesized compounds were evaluated with HepG2.2.15 cells in vitro. Results showed that most of compounds exhibited low cytotoxicity on HepG2.2.15 cells and significant inhibition on the secretion of HBsAg and HBeAg. Among them, compound 5c-1 showed the most potent activity on inhibiting HBsAg secretion (IC50 = 39.93 μM, SI = 28.51). Results of the bioactive screening showed that stronger the compounds bound to target human leukocyte antigen A protein in docking, the more active they were in anti-HBV activities in vitro.

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Resistance to lamivudine therapy: is there more than meets the eye?

Cited by 6 publications

References 29 publications

Poor response to 18‐month lamivudine monotherapy in chronic hepatitis B patients with IgM anti‐HBc and acute exacerbation

Poor response to 18‐month lamivudine monotherapy in chronic hepatitis B patients with IgM anti‐HBc and acute exacerbation

Design, Synthesis, and Bioactive Screen In Vitro of Cyclohexyl (E)-4-(Hydroxyimino)-4-Phenylbutanoates and Their Ethers for Anti-Hepatitis B Virus Agents

Discovery of Oxime Ethers as Hepatitis B Virus (HBV) Inhibitors by Docking, Screening and In Vitro Investigation

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