The zero-trans influx of uridine in human erythrocytes is inhibited by lidoflazine and analogs thereof. The concentrations required for inhibition of nucleoside transport were higher when the compounds were simultaneously added with uridine than upon preincubation of the inhibitors with the erythrocytes. R70380 proved to be the most active compound in this respect, its IC50 value being 13 nM after preincubation. Even the reference compounds nitrobenzylthioinosine and dilazep were remarkably more potent with preincubation; dipyridamole, however, was not.
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http://dx.doi.org/10.1016/0922-4106(90)90040-5 | DOI Listing |
Epigenetics
December 2025
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
RNA N6-methyladenosine (m6A) plays diverse roles in RNA metabolism and its deregulation contributes to tumor initiation and progression. Clear cell renal cell carcinoma (ccRCC) is characterized by near ubiquitous loss of followed by mutations in epigenetic regulators , , and . Mutations in , a histone H3 lysine 36 trimethylase (H3K36me3), are associated with reduced survival, greater metastatic propensity, and metabolic reprogramming.
View Article and Find Full Text PDFHepatol Int
January 2025
Department of Virology II, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo, 162-8640, Japan.
Background And Aims: Hepatitis B virus (HBV) is prevalent worldwide and is difficult to eradicate. Current treatment strategies for chronic hepatitis B ultimately seek to achieve functional cure (FC); however, the factors contributing to FC remain unclear. We aimed to investigate the gut microbiota profiles of patients with chronic hepatitis B who achieved FC.
View Article and Find Full Text PDFBioorg Med Chem Lett
January 2025
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, 250012 Jinan, Shandong, China. Electronic address:
Nucleoside analogs (NAs), as antiviral drugs, play a significant role in clinical medicine, constituting approximately 50 % of all antiviral therapies in current use. Nucleoside inhibitors function by mimicking the structure of natural nucleosides, integrating themselves into viral genetic material during replication, and subsequently inhibiting the virus's ability to reproduce. They are used to treat a variety of viral infections, including herpes simplex, hepatitis B, and acquired immunodeficiency syndrome (AIDS).
View Article and Find Full Text PDFViruses
January 2025
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon.
Islatravir (ISL) is a novel antiretroviral that inhibits HIV-1 reverse transcriptase translocation. The M184V mutation, known to reduce ISL's viral susceptibility in vitro, could arise from prolonged exposure to nucleoside reverse transcriptase inhibitors (NRTI) (3TC). This study evaluated the predictive efficacy of ISL and identified potentially active antiretrovirals in combination among treatment-experienced patients in Cameroon, where NRTIs (3TC) have been the backbone of ART for decades now.
View Article and Find Full Text PDFViruses
December 2024
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, San Diego, CA 92093-0657, USA.
Dengue, West Nile, Zika, Yellow fever, and Japanese encephalitis viruses persist as significant global health threats. The development of new therapeutic strategies based on inhibiting essential viral enzymes or viral-host protein interactions is problematic due to the fast mutation rate and rapid emergence of drug resistance. This study focuses on the NS2B-NS3 protease as a promising target for antiviral drug development.
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