Inhibitor selectivity of CNTs and ENTs

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Balázs VaskóPeter Krajcsi

Abstract

The concentrative nucleoside transporters (CNT; solute carrier family 28 (SLC28)) and the equilibrative nucleoside transporters (ENT; solute carrier family 29 (SLC29)) are important therapeutic targets but may also mediate toxicity or adverse events. To explore the relative role of the base and the monosaccharide moiety in inhibitor selectivity we selected compounds that either harbor an arabinose moiety or a cytosine moiety, as these groups had several commercially available drug members. The screening data showed that more compounds harboring a cytosine moiety displayed potent interactions with the CNTs than compounds harboring the arabinose moiety. In contrast, ENTs showed a preference for compounds with an arabinose moiety. The correlation between CNT1 and CNT3 was good as five of six compounds displayed IC50 values within the threefold threshold and one displayed a borderline 4-fold difference. For CNT1 and CNT2 as well as for CNT2 and CNT3 only two of six IC50 values correlated and one displayed a borderline 4-fold difference. Interestingly, of the six compounds that potently interacted with both ENT1 and ENT2 only nelarabine displayed selectivity. Our data show differences between inhibitor selectivities of CNTs and ENTs...Continue Reading

References

Jan 16, 1999·The Journal of Biological Chemistry·J Wang, K M Giacomini
Feb 13, 2001·Biochemical and Biophysical Research Communications·M PennycookeI R Coe
Feb 15, 2001·American Journal of Physiology. Gastrointestinal and Liver Physiology·L Y NgoJ D Unadkat
Jan 23, 2004·Leukemia·M Pastor-AngladaJ Gil
Feb 24, 2004·Molecular Pharmacology·C ChangJ D Unadkat
Mar 19, 2004·Journal of Medicinal Chemistry·Richard A FriesnerPeter S Shenkin
Mar 19, 2004·Journal of Medicinal Chemistry·Thomas A HalgrenJay L Banks
Jul 11, 2006·Biochemical and Biophysical Research Communications·Katsuhito NagaiSadaki Fujimoto
Apr 25, 2007·Molecular Membrane Biology·Kyla M SmithJames D Young
Sep 1, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Rajgopal GovindarajanJashvant D Unadkat
Jul 19, 2008·American Journal of Physiology. Gastrointestinal and Liver Physiology·Rajgopal GovindarajanJashvant D Unadkat
Feb 3, 2011·Medicinal Research Reviews·Pedro Cano-Soldado, Marçal Pastor-Anglada
Jul 29, 2011·The Journal of Biological Chemistry·Sylvia Y M YaoJames D Young
Dec 3, 2011·Nucleosides, Nucleotides & Nucleic Acids·Paula X Fernández-CalottiMarçal Pastor-Anglada
Feb 24, 2012·Nucleosides, Nucleotides & Nucleic Acids·Vijaya L DamarajuZeen Tong
Apr 19, 2012·Expert Opinion on Drug Metabolism & Toxicology·Christopher A KoczorWilliam Lewis
Aug 4, 2012·Future Medicinal Chemistry·Jung-Suk Choi, Anthony J Berdis
Mar 20, 2013·Molecular Aspects of Medicine·James D YoungStephen A Baldwin
Apr 17, 2013·Clinical Pharmacology and Therapeutics·K M HillgrenUNKNOWN International Transporter Consortium
Jul 16, 2014·World Journal of Gastroenterology : WJG·Stina NordhRoland Andersson
Dec 19, 2014·Molecular Cancer Therapeutics·Vijaya L DamarajuMichael B Sawyer
Feb 26, 2015·Frontiers in Pharmacology·Marçal Pastor-Anglada, Sandra Pérez-Torras
Aug 4, 2015·Biological & Pharmaceutical Bulletin·Kumiko UedaSeigo Iwakawa

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Hong LuCurtis Klaassen
The Journal of Pharmacology and Experimental Therapeutics
Ryo KatoIkumi Tamai
Frontiers in Pharmacology
Marçal Pastor-Anglada, S Pérez-Torras
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
José García-ManteigaMarçal Pastor-Anglada
© 2022 Meta ULC. All rights reserved