Detail Information of Exogenous Modulation

General Information of Drug Transporter (DT)
DT ID DTD0245 Transporter Info
Gene Name SLC28A2
Transporter Name Concentrative nucleoside transporter 2
Gene ID
9153
UniProt ID
O43868
Exogenous factors (drugs, dietary constituents, etc.) Modulation of This DT (EGM)

Chemical Compound

  DT Modulation1

 SLC28A2 protein results in increased transport of Adenosine [9]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 SLC28A2 protein results in increased transport of Uridine [9]

Regulation Mechanism

 Transcription Factor Info

  DT Modulation1

 Benzo(a)pyrene results in increased methylation of SLC28A2 promoter [12]

Regulation Mechanism

 Transcription Factor Info

  Okadaic Acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Okadaic Acid results in decreased expression of SLC28A2 mRNA [13]

Regulation Mechanism

 Transcription Factor Info

  Purine Nucleosides

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 SLC28A2 protein results in increased transport of Purine Nucleosides [9]

Regulation Mechanism

 Transcription Factor Info

  Sodium

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 SLC28A2 protein results in increased transport of Sodium [9]

Regulation Mechanism

 Transcription Factor Info

Mycotoxins

  Aflatoxin B1

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Aflatoxin B1 results in increased methylation of SLC28A2 gene [10]

Regulation Mechanism

 Transcription Factor Info

Natural Product

  Resveratrol

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Plant Extracts co-treated with Resveratrol results in decreased expression of SLC28A2 mRNA [14]

Regulation Mechanism

 Transcription Factor Info

Approved Drug

  Trichostatin A

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Trichostatin A inhibits histone deacetylase, which then enhances Cladribine's transportation via increasing the histone acethylation level of SLC28A2 [1]

Affected Drug/Substrate

 Cladribine Modulation Type Inducer

Cell System

 CRC cell lines HCT15 and HT29

  Floxuridine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Floxuridine inhibits the transportation of Inosine by SLC28A2 [2]

Affected Drug/Substrate

 Inosine Modulation Type Inhibition

Cell System

 Monkey kidney tissue Fibroblast-like cell lines (COS)7-CNT2

  Adenosine

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Adenosine inhibits the transportation of Uridine by SLC28A2 [3]

Affected Drug/Substrate

 Uridine Modulation Type Inhibition

  Carbamazepine

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Carbamazepine affects the expression of SLC28A2 [4]

  Valproic Acid

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Valproic Acid increases the expression of SLC28A2 [5]

  Acetaminophen

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Acetaminophen increases the expression of SLC28A2 [6]

  Uridine

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Uridine inhibits the activity of SLC28A2 [3]

Drug in Preclinical Test

  (+)-JQ1

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 (+)-JQ1 inhibits the expression of SLC28A2 [7]

Discontinued Drug

  Tecadenoson

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Tecadenoson inhibits the transportation of Uridine by SLC28A2 [3]

Affected Drug/Substrate

 Uridine Modulation Type Inhibition

Investigative Drug

  Phlorizin

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Phlorizin inhibits the transportation of Inosine by SLC28A2 [2]

Affected Drug/Substrate

 Inosine Modulation Type Inhibition

Cell System

 Monkey kidney tissue Fibroblast-like cell lines (COS)7-CNT2

Carcinogen

  Benzo(a)pyrene

            2 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Benzo(a)pyrene inhibits the expression of SLC28A2 [8]

  Arsenic

            1 DT Activity Modulations Related to This Exogenous Factor Click to Show/Hide the Full List

  DT Modulation1

 Arsenic affects the methylation of SLC28A2 gene [11]

Regulation Mechanism

 Transcription Factor Info
References
1 Inhibition of histone deacetylase 7 reverses concentrative nucleoside transporter 2 repression in colorectal cancer by up-regulating histone acetylation state. Br J Pharmacol. 2018 Nov;175(22):4209-4217.
2 Identification of 8-aminoadenosine derivatives as a new class of human concentrative nucleoside transporter 2 inhibitors. ACS Med Chem Lett. 2015 Jan 28;6(3):244-8.
3 Transport of A1 adenosine receptor agonist tecadenoson by human and mouse nucleoside transporters: evidence for blood-brain barrier transport by murine equilibrative nucleoside transporter 1 mENT1. Drug Metab Dispos. 2013 Apr;41(4):916-22.
4 Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20.
5 Stem Cell Transcriptome Responses and Corresponding Biomarkers That Indicate the Transition from Adaptive Responses to Cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
6 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
7 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
8 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297.
9 Molecular cloning, functional expression and chromosomal localization of a cDNA encoding a human Na+/nucleoside cotransporter (hCNT2) selective for purine nucleosides and uridine. Mol Membr Biol. 1998;15(4):203-11.
10 Aflatoxin B1 induces persistent epigenomic effects in primary human hepatocytes associated with hepatocellular carcinoma. Toxicology. 2016 Mar 28;350-352:31-9.
11 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106.
12 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017;8(1):1369-1391.
13 A multi-omics approach to elucidate okadaic acid-induced changes in human HepaRG hepatocarcinoma cells. Arch Toxicol. 2024;98(9):2919-2935.
14 One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res. 2013;72:69-82.

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