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Basic Characteristics of Mutations
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Mutation Site
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M204V |
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Mutation Site Sentence
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Novel 2'-fluoro-6'-methylene-carbocyclic adenosine (FMCA) monophosphate prodrug (FMCAP) was synthesized and evaluated for its in vitro anti-HBV potency against a lamivudine-entecavir resistant clone (L180M+M204V+S202G). |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RT |
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Standardized Encoding Gene
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P
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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-
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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Lamivudine(LAM);Entecavir(ETV) |
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Location
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- |
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Literature Information
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PMID
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23237841
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Title
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2'-Fluoro-6'-methylene-carbocyclic adenosine phosphoramidate (FMCAP) prodrug: in vitro anti-HBV activity against the lamivudine-entecavir resistant triple mutant and its mechanism of action
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Author
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Rawal RK,Singh US,Chavre SN,Wang J,Sugiyama M,Hung W,Govindarajan R,Korba B,Tanaka Y,Chu CK
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Journal
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Bioorganic & medicinal chemistry letters
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Journal Info
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2013 Jan 15;23(2):503-6
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Abstract
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Novel 2'-fluoro-6'-methylene-carbocyclic adenosine (FMCA) monophosphate prodrug (FMCAP) was synthesized and evaluated for its in vitro anti-HBV potency against a lamivudine-entecavir resistant clone (L180M+M204V+S202G). FMCA demonstrated significant antiviral activity against wild-type as well as lamivudine-entecavir resistant triple mutant (L180M+M204V+S202G). The monophosphate prodrug (FMCAP) demonstrated greater than 12-fold (12x) increase in anti-HBV activity without increased cellular toxicity. Mitochondrial and cellular toxicity studies of FMCA indicated that there is no significant toxicity up to 100 muM. Mode of action studies by molecular modeling indicate that the 2'-fluoro moiety by hydrogen bond as well as the Van der Waals interaction of the carbocyclic ring with the phenylalanine moiety of the polymerase promote the positive binding, even in the drug-resistant mutants.
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Sequence Data
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-
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