Investigation of the main pharmacokinetic parameters of adenine derivative VMA-99-82 in rats showed large values of the half-life (T1/2 = 11.03 h) and the mean retention time of drug molecules in the organism (MRT = 9.53 h). A high rate of the drug concentration decrease in the plasma determines a small value of the area under the pharmacokinetic curve (AUC = 74.96 mg h/ml). The total distribution volume (V(d) = 10.61 l/kg) is 15.8 times greater than the volume of extracellular fluid in the body of rat, which is indicative of a high ability of VMA-99-82 to be distributed and accumulated in the organs and tissues. The absolute bioavailability of VMA-99-82 is 66%.
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J Med Virol
February 2025
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea.
While entecavir (ETV) and tenofovir disoproxil fumarate (TDF) effectively manage chronic hepatitis B, their long-term effects on lipid metabolism and cardiovascular outcomes remain unclear. This study compares the impact of ETV, TDF, and treatment-naïve (control group) on hyperlipidemia and major adverse cardiac events (MACE) in people living with chronic hepatitis B (PLWHB). We used claim data from the South Korean National Health Insurance Service.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
MOE Key Laboratory of Evolution & Marine Biodiversity and Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao 266003, China.
DNA N6-methyladenine (6mA) is a potential epigenetic mark involved in gene transcription in eukaryotes, yet the regulatory mechanism governing its methyltransferase (MTase) activity remains obscure. Here, we exploited the 6mA MTase AMT1 to elucidate its auto-regulation in the unicellular eukaryote Tetrahymena thermophila. The detailed endogenous localization of AMT1 in vegetative and sexual stages revealed a correlation between the 6mA reestablishment in the new MAC and the occurrence of zygotically expressed AMT1.
View Article and Find Full Text PDFFront Physiol
January 2025
Walther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany.
Two-pore channels (TPCs) are adenine nucleotide and phosphoinositide regulated cation channels. NAADP activates and ATP blocks TPCs, while the endolysosomal phosphoinositide PI(3,5)P activates TPCs. TPCs are ubiquitously expressed including expression in the innate as well as the adaptive immune system.
View Article and Find Full Text PDFChem Commun (Camb)
January 2025
Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Korea.
1,4-Dihydronicotinamide adenine dinucleotide (NADH) and its phosphate ester (NADPH) are essential cofactors required for all living cells, playing pivotal roles in multiple biological processes such as energy metabolism and biosynthesis. NADPH is produced during photosynthesis by the combination of photosystem II, where water is oxidised, and photosystem I, where NADP is reduced. This review focuses on catalytic NAD(P) (and its analogues) reduction to generate 1,4-NAD(P)H without formation of other regioisomers and the dimer.
View Article and Find Full Text PDFBiochemistry (Mosc)
December 2024
National Research Centre "Kurchatov Institute", Moscow, 123182, Russia.
Bacterial and viral RNA polymerases are promising targets for the development of new transcription inhibitors. One of the potential blockers of RNA synthesis is 7,8-dihydro-8-oxo-1,-ethenoadenine (oxo-εA), a synthetic compound that combines two adenine modifications: 8-oxoadenine and 1,-ethenoadenine. In this study, we synthesized oxo-εA triphosphate (oxo-εATP) and showed that it could be incorporated by the RNA-dependent RNA polymerase of SARS-CoV-2 into synthesized RNA opposite template residues A and G in the presence of Mn ions.
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