FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3111010243> ?p ?o ?g. }

• W3111010243 endingPage "1086" @default.
• W3111010243 startingPage "1075" @default.
• W3111010243 abstract "While certain nucleos(t)ide reverse transcriptase inhibitors (NRTIs) are efficacious in treating HBV infection, their effects are yet to be optimized and the emergence of NRTI-resistant HBV variants is an issue because of the requirement for lifelong treatment. The development of agents that more profoundly suppress wild-type and drug-resistant HBVs, and that have a long-acting effect, are crucial to improve patient outcomes.Herein, we synthesized a novel long-acting 4'-modified NRTI termed E-CFCP. We tested its anti-HBV activity in vitro, before evaluating its anti-HBV activity in HBV-infected human-liver-chimeric mice (PXB-mice). E-CFCP's long-acting features and E-CFCP-triphosphate's interactions with the HBV reverse transcriptase (HBV-RT) were examined.E-CFCP potently blocked HBVWTD1 production (IC50qPCR_cell=1.8 nM) in HepG2.2.15 cells and HBVWTC2 (IC50SB_cell=0.7 nM), entecavir (ETV)-resistant HBVETV-RL180M/S202G/M204V (IC50SB_cell=77.5 nM), and adefovir-resistant HBVADV-RA181T/N236T production (IC50SB_cell=14.1 nM) in Huh7 cells. E-CFCP profoundly inhibited intracellular HBV DNA production to below the detection limit, but ETV and tenofovir alafenamide (TAF) failed to do so. E-CFCP also showed less toxicity than ETV and TAF. E-CFCP better penetrated hepatocytes and was better tri-phosphorylated; E-CFCP-triphosphate persisted intracellularly for longer than ETV-triphosphate. Once-daily peroral E-CFCP administration over 2 weeks (0.02~0.2 mg/kg/day) reduced HBVWTC2-viremia by 2-3 logs in PXB-mice without significant toxicities and the reduction persisted over 1-3 weeks following treatment cessation, suggesting once-weekly dosing capabilities. E-CFCP also reduced HBVETV-RL180M/S202G/M204V-viremia by 2 logs over 2 weeks, while ETV completely failed to reduce HBVETV-RL180M/S202G/M204V-viremia. E-CFCP's 4'-cyano and fluorine interact with both HBVWT-RT and HBVETV-RL180M/S202G-M204 -RT via Van der Waals and polar forces, being important for E-CFCP-triphosphate's interactions and anti-HBV potency.E-CFCP represents the first reported potential long-acting NRTI with potent activity against wild-type and treatment-resistant HBV.Although there are currently effective treatment options for HBV, treatment-resistant variants and the need for lifelong therapy pose a significant challenge. Therefore, the development of new treatment options is crucial to improve outcomes and quality of life. Herein, we report preclinical evidence showing that the anti-HBV agent, E-CFCP, has potent activity against wild-type and treatment-resistant variants. In addition, once-weekly oral dosing may be possible, which is preferrable to the current daily dosing regimens." @default.
• W3111010243 created "2020-12-21" @default.
• W3111010243 creator A5007062297 @default.
• W3111010243 creator A5009887722 @default.
• W3111010243 creator A5012018663 @default.
• W3111010243 creator A5020266861 @default.
• W3111010243 creator A5024024043 @default.
• W3111010243 creator A5026222199 @default.
• W3111010243 creator A5030756908 @default.
• W3111010243 creator A5034448543 @default.
• W3111010243 creator A5037650438 @default.
• W3111010243 creator A5047248018 @default.
• W3111010243 creator A5058961574 @default.
• W3111010243 creator A5061192533 @default.
• W3111010243 creator A5075530794 @default.
• W3111010243 creator A5080757983 @default.
• W3111010243 creator A5082484825 @default.
• W3111010243 creator A5085363259 @default.
• W3111010243 creator A5087167224 @default.
• W3111010243 date "2021-05-01" @default.
• W3111010243 modified "2023-10-15" @default.
• W3111010243 title "Identification of a novel long-acting 4’-modified nucleoside reverse transcriptase inhibitor against HBV" @default.
• W3111010243 cites W1834860141 @default.
• W3111010243 cites W1985977968 @default.
• W3111010243 cites W1991249891 @default.
• W3111010243 cites W2001604203 @default.
• W3111010243 cites W2056599541 @default.
• W3111010243 cites W2069799026 @default.
• W3111010243 cites W2103562758 @default.
• W3111010243 cites W2138764171 @default.
• W3111010243 cites W2156631886 @default.
• W3111010243 cites W2416145957 @default.
• W3111010243 cites W2481374159 @default.
• W3111010243 cites W2486192779 @default.
• W3111010243 cites W2521275619 @default.
• W3111010243 cites W2917955650 @default.
• W3111010243 cites W2924803014 @default.
• W3111010243 cites W2947049598 @default.
• W3111010243 cites W2954286059 @default.
• W3111010243 cites W2982613471 @default.
• W3111010243 doi "https://doi.org/10.1016/j.jhep.2020.12.006" @default.
• W3111010243 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33333207" @default.
• W3111010243 hasPublicationYear "2021" @default.
• W3111010243 type Work @default.
• W3111010243 sameAs 3111010243 @default.
• W3111010243 citedByCount "19" @default.
• W3111010243 countsByYear W31110102432021 @default.
• W3111010243 countsByYear W31110102432022 @default.
• W3111010243 countsByYear W31110102432023 @default.
• W3111010243 crossrefType "journal-article" @default.
• W3111010243 hasAuthorship W3111010243A5007062297 @default.
• W3111010243 hasAuthorship W3111010243A5009887722 @default.
• W3111010243 hasAuthorship W3111010243A5012018663 @default.
• W3111010243 hasAuthorship W3111010243A5020266861 @default.
• W3111010243 hasAuthorship W3111010243A5024024043 @default.
• W3111010243 hasAuthorship W3111010243A5026222199 @default.
• W3111010243 hasAuthorship W3111010243A5030756908 @default.
• W3111010243 hasAuthorship W3111010243A5034448543 @default.
• W3111010243 hasAuthorship W3111010243A5037650438 @default.
• W3111010243 hasAuthorship W3111010243A5047248018 @default.
• W3111010243 hasAuthorship W3111010243A5058961574 @default.
• W3111010243 hasAuthorship W3111010243A5061192533 @default.
• W3111010243 hasAuthorship W3111010243A5075530794 @default.
• W3111010243 hasAuthorship W3111010243A5080757983 @default.
• W3111010243 hasAuthorship W3111010243A5082484825 @default.
• W3111010243 hasAuthorship W3111010243A5085363259 @default.
• W3111010243 hasAuthorship W3111010243A5087167224 @default.
• W3111010243 hasBestOaLocation W31110102431 @default.
• W3111010243 hasConcept C104317684 @default.
• W3111010243 hasConcept C142462285 @default.
• W3111010243 hasConcept C153911025 @default.
• W3111010243 hasConcept C156719811 @default.
• W3111010243 hasConcept C159047783 @default.
• W3111010243 hasConcept C202751555 @default.
• W3111010243 hasConcept C2522874641 @default.
• W3111010243 hasConcept C2776175608 @default.
• W3111010243 hasConcept C2776185481 @default.
• W3111010243 hasConcept C2776543447 @default.
• W3111010243 hasConcept C2777333352 @default.
• W3111010243 hasConcept C2777869810 @default.
• W3111010243 hasConcept C2779517838 @default.
• W3111010243 hasConcept C2780593183 @default.
• W3111010243 hasConcept C2911190787 @default.
• W3111010243 hasConcept C2993143319 @default.
• W3111010243 hasConcept C55493867 @default.
• W3111010243 hasConcept C67705224 @default.
• W3111010243 hasConcept C86803240 @default.
• W3111010243 hasConceptScore W3111010243C104317684 @default.
• W3111010243 hasConceptScore W3111010243C142462285 @default.
• W3111010243 hasConceptScore W3111010243C153911025 @default.
• W3111010243 hasConceptScore W3111010243C156719811 @default.
• W3111010243 hasConceptScore W3111010243C159047783 @default.
• W3111010243 hasConceptScore W3111010243C202751555 @default.
• W3111010243 hasConceptScore W3111010243C2522874641 @default.
• W3111010243 hasConceptScore W3111010243C2776175608 @default.
• W3111010243 hasConceptScore W3111010243C2776185481 @default.
• W3111010243 hasConceptScore W3111010243C2776543447 @default.
• W3111010243 hasConceptScore W3111010243C2777333352 @default.

• next