Inhibitor selectivity of CNTs and ENTs

Balázs Vaskó, Viktória Juhász, Beáta Tóth, Anita Kurunczi, Zsolt Fekete, Joseph Krisjanis Zolnerciks, Emese Kis, Rémi Magnan, Axel Bidon-Chanal Badia, Marçal Pastor-Anglada, Eszter Hazai, Zsolt Bikadi, F. Fülöp, Peter Krajcsi

Research output: Contribution to journalArticle

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 as well as differences within the CNT family members.

Original languageEnglish
JournalXenobiotica
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Arabinose
Nucleoside Transport Proteins
Cytosine
Inhibitory Concentration 50
Monosaccharides
Ports and harbors
Toxicity
Screening
Pharmaceutical Preparations
Therapeutics

Keywords

  • antiviral drug
  • chemotherapy drug
  • Concentrative nucleoside transporter
  • equilibrative nucleoside transporter
  • IC value
  • nucleoside analog

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

Cite this

Vaskó, B., Juhász, V., Tóth, B., Kurunczi, A., Fekete, Z., Krisjanis Zolnerciks, J., ... Krajcsi, P. (Accepted/In press). Inhibitor selectivity of CNTs and ENTs. Xenobiotica. https://doi.org/10.1080/00498254.2018.1501832

Inhibitor selectivity of CNTs and ENTs. / Vaskó, Balázs; Juhász, Viktória; Tóth, Beáta; Kurunczi, Anita; Fekete, Zsolt; Krisjanis Zolnerciks, Joseph; Kis, Emese; Magnan, Rémi; Bidon-Chanal Badia, Axel; Pastor-Anglada, Marçal; Hazai, Eszter; Bikadi, Zsolt; Fülöp, F.; Krajcsi, Peter.

In: Xenobiotica, 01.01.2018.

Research output: Contribution to journalArticle

Vaskó, B, Juhász, V, Tóth, B, Kurunczi, A, Fekete, Z, Krisjanis Zolnerciks, J, Kis, E, Magnan, R, Bidon-Chanal Badia, A, Pastor-Anglada, M, Hazai, E, Bikadi, Z, Fülöp, F & Krajcsi, P 2018, 'Inhibitor selectivity of CNTs and ENTs', Xenobiotica. https://doi.org/10.1080/00498254.2018.1501832
Vaskó B, Juhász V, Tóth B, Kurunczi A, Fekete Z, Krisjanis Zolnerciks J et al. Inhibitor selectivity of CNTs and ENTs. Xenobiotica. 2018 Jan 1. https://doi.org/10.1080/00498254.2018.1501832
Vaskó, Balázs ; Juhász, Viktória ; Tóth, Beáta ; Kurunczi, Anita ; Fekete, Zsolt ; Krisjanis Zolnerciks, Joseph ; Kis, Emese ; Magnan, Rémi ; Bidon-Chanal Badia, Axel ; Pastor-Anglada, Marçal ; Hazai, Eszter ; Bikadi, Zsolt ; Fülöp, F. ; Krajcsi, Peter. / Inhibitor selectivity of CNTs and ENTs. In: Xenobiotica. 2018.
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